7-102749406-T-G

Position:

• chr7-102749406-T-G

Variant summary

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

The NM_001145268.2(FAM185A):​c.199T>G​(p.Trp67Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM185A NM_001145268.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.82

Genes affected

FAM185A (HGNC:22412): (family with sequence similarity 185 member A)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM185A	NM_001145268.2	c.199T>G	p.Trp67Gly	missense_variant	1/8	ENST00000413034.3	NP_001138740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM185A	ENST00000413034.3	c.199T>G	p.Trp67Gly	missense_variant	1/8	5	NM_001145268.2	ENSP00000395340	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.199T>G (p.W67G) alteration is located in exon 1 (coding exon 1) of the FAM185A gene. This alteration results from a T to G substitution at nucleotide position 199, causing the tryptophan (W) at amino acid position 67 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Benign	0.77
DEOGEN2	Benign	0.26	.;.;T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.052
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.52	T;T;T
M_CAP	Pathogenic	0.38	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Uncertain	0.096	D
MutationAssessor	Uncertain	2.6	M;.;M
MutationTaster	Benign	1.0	D;N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.3	N;D;D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.028	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.53
MutPred		0.61		Gain of disorder (P = 0.0324);Gain of disorder (P = 0.0324);Gain of disorder (P = 0.0324);
MVP		0.35
ClinPred		0.65	D
GERP RS		4.1
Varity_R		0.84
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-102389853;