6-29440944-T-G

Variant names:

• chr6-29440944-T-G
• rs11968123
• NM_013941.4:c.929T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013941.4(OR10C1):​c.929T>G​(p.Met310Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00777 in 1,604,758 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (65 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (120 hom.)
• Consequence: OR10C1 NM_013941.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.654
• Publications: 11 publications found

Genes affected

OR10C1 (HGNC:8165): (olfactory receptor family 10 subfamily C member 1) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]

OR11A1 (HGNC:8176): (olfactory receptor family 11 subfamily A member 1) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003185898).
• BP6: Variant 6-29440944-T-G is Benign according to our data. Variant chr6-29440944-T-G is described in ClinVar as Benign. ClinVar VariationId is 780982.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013941.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10C1	NM_013941.4	MANE Select	c.929T>G	p.Met310Arg	missense	Exon 1 of 1	NP_039229.3
	OR11A1	NM_001394828.1	MANE Select	c.-388-8957A>C		intron	N/A	NP_001381757.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR10C1	ENST00000444197.3	TSL:6 MANE Select	c.929T>G	p.Met310Arg	missense	Exon 1 of 1	ENSP00000419119.1
	OR11A1	ENST00000377149.5	TSL:6 MANE Select	c.-388-8957A>C		intron	N/A	ENSP00000366354.1
	OR10C1	ENST00000622521.1	TSL:6	c.935T>G	p.Met312Arg	missense	Exon 1 of 1	ENSP00000481429.1

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3149 AN: 152070 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00546

Gnomad OTH AF: 0.0245

GnomAD2 exomes AF: 0.00967 AC: 2340 AN: 241976 AF XY: 0.00840

Gnomad AFR exome AF: 0.0636

Gnomad AMR exome AF: 0.0123

Gnomad ASJ exome AF: 0.0207

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000516

Gnomad NFE exome AF: 0.00581

Gnomad OTH exome AF: 0.0113

GnomAD4 exome AF: 0.00641 AC: 9314 AN: 1452570 Hom.: 120 Cov.: 31 AF XY: 0.00621 AC XY: 4493 AN XY: 723026

African (AFR) AF: 0.0639 AC: 2131 AN: 33356

American (AMR) AF: 0.0134 AC: 597 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 555 AN: 26024

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39660

South Asian (SAS) AF: 0.00168 AC: 145 AN: 86098

European-Finnish (FIN) AF: 0.000403 AC: 20 AN: 49568

Middle Eastern (MID) AF: 0.0259 AC: 149 AN: 5754

European-Non Finnish (NFE) AF: 0.00458 AC: 5066 AN: 1107276

Other (OTH) AF: 0.0108 AC: 649 AN: 60178

GnomAD4 genome AF: 0.0207 AC: 3156 AN: 152188 Hom.: 65 Cov.: 32 AF XY: 0.0194 AC XY: 1446 AN XY: 74416

African (AFR) AF: 0.0587 AC: 2439 AN: 41526

American (AMR) AF: 0.0135 AC: 206 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4822

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00546 AC: 371 AN: 67986

Other (OTH) AF: 0.0242 AC: 51 AN: 2104

Alfa AF: 0.0108 Hom.: 71

Bravo AF: 0.0237

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.0603 AC: 182

ESP6500EA AF: 0.00720 AC: 39

ExAC AF: 0.00969 AC: 1151

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.00676

EpiControl AF: 0.00717

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.0
DANN	Benign	0.56
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.030	N
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		-0.65
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.028
Sift	Benign	0.11	T
Polyphen		0.012	B
MVP		0.014
MPC		0.52
ClinPred		0.00030	T
GERP RS		0.082
Varity_R		0.17
gMVP		0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11968123; hg19: chr6-29408721;