7-141919663-A-C

Variant names:

• chr7-141919663-A-C
• rs556697772
• NM_001001656.3:c.788A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001656.3(OR9A4):​c.788A>C​(p.Lys263Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: OR9A4 NM_001001656.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

Genes affected

OR9A4 (HGNC:15095): (olfactory receptor family 9 subfamily A member 4) 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]

MGAM (HGNC:7043): (maltase-glucoamylase) This gene encodes maltase-glucoamylase, which is a brush border membrane enzyme that plays a role in the final steps of digestion of starch. The protein has two catalytic sites identical to those of sucrase-isomaltase, but the proteins are only 59% homologous. Both are members of glycosyl hydrolase family 31, which has a variety of substrate specificities. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0705564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR9A4	NM_001001656.3	c.788A>C	p.Lys263Thr	missense_variant	Exon 2 of 2	ENST00000641559.1	NP_001001656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR9A4	ENST00000641559.1	c.788A>C	p.Lys263Thr	missense_variant	Exon 2 of 2		NM_001001656.3	ENSP00000493151.1
OR9A4	ENST00000548136.1	c.788A>C	p.Lys263Thr	missense_variant	Exon 1 of 1	6		ENSP00000448789.1
MGAM	ENST00000465654.5	c.-180+11795A>C		intron_variant	Intron 1 of 5	3		ENSP00000419372.1
MGAM	ENST00000497554.1	n.37-10114A>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74336

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.37	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.6	.;N
REVEL	Benign	0.078
Sift	Benign	0.10	.;T
Sift4G	Benign	0.31	.;T
Polyphen		0.056	B;B
Vest4		0.13
MutPred		0.50		Loss of ubiquitination at K263 (P = 0.0233);Loss of ubiquitination at K263 (P = 0.0233);
MVP		0.54
MPC		0.26
ClinPred		0.29	T
GERP RS		2.6
Varity_R		0.086
gMVP		0.11

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

Publications

LitVar

Other links and lift over

dbSNP: rs556697772; hg19: chr7-141619463;