7-102751706-T-C

Variant names:

• chr7-102751706-T-C
• NM_001145268.2:c.466T>C

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.466T>C​(p.Ser156Pro) 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: 28)
• Consequence: FAM185A NM_001145268.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92
• 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=0.18833861).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM185A	NM_001145268.2	c.466T>C	p.Ser156Pro	missense_variant	Exon 2 of 8	ENST00000413034.3	NP_001138740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM185A	ENST00000413034.3	c.466T>C	p.Ser156Pro	missense_variant	Exon 2 of 8	5	NM_001145268.2	ENSP00000395340.2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 28

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.466T>C (p.S156P) alteration is located in exon 2 (coding exon 2) of the FAM185A gene. This alteration results from a T to C substitution at nucleotide position 466, causing the serine (S) at amino acid position 156 to be replaced by a proline (P). 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	0.64
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	.;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.077
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.0	.;M
PhyloP100		1.9
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.8	D;N
REVEL	Benign	0.13
Sift	Benign	0.053	T;T
Sift4G	Uncertain	0.052	T;D
Polyphen		0.90	.;P
Vest4		0.58
MutPred		0.33		Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);
MVP		0.13
ClinPred		0.97	D
GERP RS		1.2
Varity_R		0.30
gMVP		0.70
Mutation Taster		=41/59	disease causing

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: chr7-102392153;