rs760941149

Variant names:

• chr11-6481545-A-C
• rs760941149
• NM_012192.4:c.29A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-6481545-A-C
• chr11-6481545-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_012192.4(TIMM10B):​c.29A>C​(p.Gln10Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,458,518 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: TIMM10B NM_012192.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54
• Publications: 1 publications found

Genes affected

TIMM10B (HGNC:4022): (translocase of inner mitochondrial membrane 10B) FXC1, or TIMM10B, belongs to a family of evolutionarily conserved proteins that are organized in heterooligomeric complexes in the mitochondrial intermembrane space. These proteins mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane.[supplied by OMIM, Apr 2004]

ENSG00000283977 (HGNC:):

ARFIP2 (HGNC:17160): (ADP ribosylation factor interacting protein 2) Enables several functions, including GTP-dependent protein binding activity; membrane curvature sensor activity; and phosphatidylinositol-4-phosphate binding activity. Involved in actin cytoskeleton organization. Located in cell cortex; ruffle; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012192.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMM10B	NM_012192.4	MANE Select	c.29A>C	p.Gln10Pro	missense	Exon 1 of 3	NP_036324.1	Q9Y5J6
	ARFIP2	NM_001376558.2	MANE Select	c.-357T>G		upstream_gene	N/A	NP_001363487.1	P53365-1
	ARFIP2	NM_001242854.3		c.-357T>G		upstream_gene	N/A	NP_001229783.1	A0A087X1E4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMM10B	ENST00000254616.11	TSL:1 MANE Select	c.29A>C	p.Gln10Pro	missense	Exon 1 of 3	ENSP00000254616.6	Q9Y5J6
	TIMM10B	ENST00000528908.1	TSL:1	n.45A>C		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000283977	ENST00000640959.1	TSL:4	n.29A>C		non_coding_transcript_exon	Exon 1 of 5	ENSP00000491841.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000249 AC: 6 AN: 240514 AF XY: 0.0000231

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000178

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000549 AC: 8 AN: 1458518 Hom.: 0 Cov.: 33 AF XY: 0.00000414 AC XY: 3 AN XY: 725140

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.000159 AC: 7 AN: 44124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25968

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 85362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110766

Other (OTH) AF: 0.00 AC: 0 AN: 60306

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	1.9	L
PhyloP100		3.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.91	P
Vest4		0.55
MutPred		0.71		Gain of glycosylation at Q10 (P = 0.0347)
MVP		0.72
MPC		0.44
ClinPred		0.78	D
GERP RS		5.1
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.97
gMVP		0.88
Mutation Taster		=78/22	polymorphism

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: rs760941149; hg19: chr11-6502775;