7-102749316-A-G

Variant names:

• chr7-102749316-A-G
• NM_001145268.2:c.109A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145268.2(FAM185A):​c.109A>G​(p.Arg37Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM185A NM_001145268.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.167
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25494307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM185A	NM_001145268.2	c.109A>G	p.Arg37Gly	missense_variant	Exon 1 of 8	ENST00000413034.3	NP_001138740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM185A	ENST00000413034.3	c.109A>G	p.Arg37Gly	missense_variant	Exon 1 of 8	5	NM_001145268.2	ENSP00000395340.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.109A>G (p.R37G) alteration is located in exon 1 (coding exon 1) of the FAM185A gene. This alteration results from a A to G substitution at nucleotide position 109, causing the arginine (R) at amino acid position 37 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	Benign	0.077
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.039	.;.;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.3	M;.;M
PhyloP100		-0.17
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.82	N;N;N
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.023	B;.;B
Vest4		0.24
MutPred		0.52		Loss of MoRF binding (P = 0.0195);Loss of MoRF binding (P = 0.0195);Loss of MoRF binding (P = 0.0195);
MVP		0.16
ClinPred		0.87	D
GERP RS		-2.8
PromoterAI		-0.086	Neutral
Varity_R		0.15
gMVP		0.68
Mutation Taster		=99/1	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

hg19: chr7-102389763;