Variant 7-102808313-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145268.2(FAM185A):c.1090C>T(p.Arg364Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000753 in 1,551,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 0 hom. )

Consequence

FAM185A
NM_001145268.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0160

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009459853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM185A	NM_001145268.2 linkuse as main transcript	c.1090C>T	p.Arg364Cys	missense_variant	8/8	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.1090C>T	p.Arg364Cys	missense_variant	8/8	5	NM_001145268.2	ENSP00000395340	P1	Q8N0U4-1
FAM185A	ENST00000409231.7 linkuse as main transcript	c.739C>T	p.Arg247Cys	missense_variant	7/7	2		ENSP00000387066		Q8N0U4-3
FAM185A	ENST00000420217.1 linkuse as main transcript	c.*633C>T		3_prime_UTR_variant, NMD_transcript_variant	8/8	2		ENSP00000400947
FAM185A	ENST00000442873.5 linkuse as main transcript	c.*633C>T		3_prime_UTR_variant, NMD_transcript_variant	8/8	2		ENSP00000410226		Q8N0U4-2

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000853

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000597

AC:

AN:

157502

Hom.:

AF XY:

0.000457

AC XY:

AN XY:

83226

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.000451

GnomAD4 exome

AF:

0.000770

AC:

1078

AN:

1399394

Hom.:

Cov.:

AF XY:

0.000732

AC XY:

505

AN XY:

690202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00326

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000126

Gnomad4 FIN exome

AF:

0.000182

Gnomad4 NFE exome

AF:

0.000848

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.000598

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000853

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000851

Hom.:

Bravo

AF:

0.000657

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.000943

AC:

ExAC

AF:

0.000515

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 19, 2023

The c.1090C>T (p.R364C) alteration is located in exon 8 (coding exon 8) of the FAM185A gene. This alteration results from a C to T substitution at nucleotide position 1090, causing the arginine (R) at amino acid position 364 to be replaced by a cysteine (C). 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

0.078

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

.;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.11

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.0095

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.10

Sift

Benign

0.046

D;T

Sift4G

Uncertain

0.026

D;D

Polyphen

0.98

D;P

Vest4

0.074

MVP

0.25

ClinPred

0.052

GERP RS

-0.43

Varity_R

0.059

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

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

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