NM_001145268.2:c.230T>C

Variant names:

• chr7-102749437-T-C
• NM_001145268.2:c.230T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001145268.2(FAM185A):​c.230T>C​(p.Leu77Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 5.56
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM185A	NM_001145268.2	c.230T>C	p.Leu77Pro	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.230T>C	p.Leu77Pro	missense_variant	Exon 1 of 8	5	NM_001145268.2	ENSP00000395340.2

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

Apr 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.230T>C (p.L77P) alteration is located in exon 1 (coding exon 1) of the FAM185A gene. This alteration results from a T to C substitution at nucleotide position 230, causing the leucine (L) at amino acid position 77 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	0.89
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.82	D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.6	.;M
PhyloP100		5.6
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	.;D
Vest4		0.85
MutPred		0.66		Gain of disorder (P = 0.0099);Gain of disorder (P = 0.0099);
MVP		0.17
ClinPred		0.99	D
GERP RS		3.9
PromoterAI		0.024	Neutral
Varity_R		0.90
gMVP		0.97
Mutation Taster		=32/68	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: chr7-102389884;