7-102751692-G-T

Variant names:

• chr7-102751692-G-T
• rs1248931505
• NM_001145268.2:c.452G>T

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.452G>T​(p.Gly151Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000052 in 1,538,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: FAM185A NM_001145268.2 missense, splice_region
• Scores: Splicing: ADA: 0.3267
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77
• 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=0.15051723).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM185A	NM_001145268.2	c.452G>T	p.Gly151Val	missense_variant, splice_region_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.452G>T	p.Gly151Val	missense_variant, splice_region_variant	Exon 2 of 8	5	NM_001145268.2	ENSP00000395340.2

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 151976 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000526 AC: 73 AN: 1386750 Hom.: 0 Cov.: 30 AF XY: 0.0000585 AC XY: 40 AN XY: 683864

African (AFR) AF: 0.0000656 AC: 2 AN: 30496

American (AMR) AF: 0.00 AC: 0 AN: 31740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24654

East Asian (EAS) AF: 0.00 AC: 0 AN: 35608

South Asian (SAS) AF: 0.00 AC: 0 AN: 76286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 0.0000632 AC: 68 AN: 1075634

Other (OTH) AF: 0.0000522 AC: 3 AN: 57478

GnomAD4 genome AF: 0.0000461 AC: 7 AN: 151976 Hom.: 0 Cov.: 28 AF XY: 0.0000269 AC XY: 2 AN XY: 74216

African (AFR) AF: 0.0000483 AC: 2 AN: 41370

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.452G>T (p.G151V) alteration is located in exon 2 (coding exon 2) of the FAM185A gene. This alteration results from a G to T substitution at nucleotide position 452, causing the glycine (G) at amino acid position 151 to be replaced by a valine (V). 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	0.24
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	.;L
PhyloP100		3.8
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.1	D;N
REVEL	Benign	0.18
Sift	Uncertain	0.013	D;D
Sift4G	Benign	0.18	T;T
Polyphen		0.72	.;P
Vest4		0.33
MutPred		0.36		Gain of sheet (P = 0.0166);Gain of sheet (P = 0.0166);
MVP		0.28
ClinPred		0.57	D
GERP RS		0.10
Varity_R		0.11
gMVP		0.37
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.33
dbscSNV1_RF	Benign	0.40
SpliceAI score (max)		0.020		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: rs1248931505; hg19: chr7-102392139;