Genetic Variant FAM185A:p.Ser44Arg (chr7-102749339-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145268.2(FAM185A):c.132C>G(p.Ser44Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,549,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

FAM185A
NM_001145268.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.42

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055138916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM185A	NM_001145268.2 link	c.132C>G	p.Ser44Arg	missense_variant	Exon 1 of 8	ENST00000413034.3	NP_001138740.2	Q8N0U4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM185A	ENST00000413034.3 link	c.132C>G	p.Ser44Arg	missense_variant	Exon 1 of 8	5	NM_001145268.2	ENSP00000395340.2		Q8N0U4-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.000220

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000653

AC:

AN:

153250

AF XY:

0.0000857

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000154

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

AF:

0.000139

AC:

194

AN:

1396998

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

689036

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31544

American (AMR)

AF:

0.00

AC:

AN:

35692

Ashkenazi Jewish (ASJ)

AF:

0.0000397

AC:

AN:

25164

East Asian (EAS)

AF:

0.00

AC:

AN:

35732

South Asian (SAS)

AF:

0.00

AC:

AN:

79148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4576

European-Non Finnish (NFE)

AF:

0.000169

AC:

182

AN:

1078692

Other (OTH)

AF:

0.000173

AC:

AN:

57830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000112

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41476

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000693

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000399

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.132C>G (p.S44R) alteration is located in exon 1 (coding exon 1) of the FAM185A gene. This alteration results from a C to G substitution at nucleotide position 132, causing the serine (S) at amino acid position 44 to be replaced by an arginine (R). 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

0.090

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.37

CADD

Benign

0.19

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.00026

.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.29

T;T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.055

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N

PhyloP100

-2.4

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.70

N;N;N

REVEL

Benign

0.085

Sift

Benign

0.083

T;T;T

Sift4G

Uncertain

0.057

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.057

MutPred

0.20

Loss of phosphorylation at S44 (P = 0.012);Loss of phosphorylation at S44 (P = 0.012);Loss of phosphorylation at S44 (P = 0.012);

MVP

0.014

ClinPred

0.037

GERP RS

-0.67

PromoterAI

0.035

Neutral

(source)

Varity_R

0.052

gMVP

0.39

Mutation Taster

=98/2

polymorphism

(source)

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

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7-102749339-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over