Variant 7-102761283-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145268.2(FAM185A):c.665T>C(p.Ile222Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000046 in 1,542,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

FAM185A
NM_001145268.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.11

Variant links:

Genes affected

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

FAM185A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1708535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM185A	NM_001145268.2 linkuse as main transcript	c.665T>C	p.Ile222Thr	missense_variant	4/8	ENST00000413034.3	NP_001138740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM185A	ENST00000413034.3 linkuse as main transcript	c.665T>C	p.Ile222Thr	missense_variant	4/8	5	NM_001145268.2	ENSP00000395340	P1	Q8N0U4-1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000491

AC:

AN:

142528

Hom.:

AF XY:

0.0000398

AC XY:

AN XY:

75446

show subpopulations

Gnomad AFR exome

AF:

0.000686

Gnomad AMR exome

AF:

0.0000491

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000249

GnomAD4 exome

AF:

0.0000273

AC:

AN:

1390196

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

685430

show subpopulations

Gnomad4 AFR exome

AF:

0.000583

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000139

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

AF:

0.000217

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.000772

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000193

ExAC

AF:

0.0000408

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.665T>C (p.I222T) alteration is located in exon 4 (coding exon 4) of the FAM185A gene. This alteration results from a T to C substitution at nucleotide position 665, causing the isoleucine (I) at amino acid position 222 to be replaced by a threonine (T). 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

0.17

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.018

.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.61

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

.;M

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.098

Sift

Uncertain

0.027

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.12

B;B

Vest4

0.68

MVP

0.067

ClinPred

0.081

GERP RS

3.0

Varity_R

0.12

gMVP

0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over