dbSNP rs1178896137: FAM171A2:p.Ala714Val (chr17-44354073-G-A) – 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_198475.3(FAM171A2):c.2141C>T(p.Ala714Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000163 in 1,105,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000075 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Consequence

FAM171A2
NM_198475.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.534

Publications

0 publications found

Variant links:

Genes affected

FAM171A2 (HGNC:30480): (family with sequence similarity 171 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM171A2 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=0.032553703).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM171A2	NM_198475.3	MANE Select	c.2141C>T	p.Ala714Val	missense	Exon 8 of 8	NP_940877.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM171A2	ENST00000293443.12	TSL:1 MANE Select	c.2141C>T	p.Ala714Val	missense	Exon 8 of 8	ENSP00000293443.6	A8MVW0
FAM171A2	ENST00000912944.1		c.2177C>T	p.Ala726Val	missense	Exon 9 of 9	ENSP00000583003.1
FAM171A2	ENST00000912945.1		c.2168C>T	p.Ala723Val	missense	Exon 8 of 8	ENSP00000583004.1

Frequencies

GnomAD3 genomes

AF:

0.0000751

AC:

AN:

146470

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00199

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000496

GnomAD4 exome

AF:

0.00000730

AC:

AN:

959172

Hom.:

Cov.:

AF XY:

0.00000887

AC XY:

AN XY:

450738

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18618

American (AMR)

AF:

0.00

AC:

AN:

4662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9202

East Asian (EAS)

AF:

0.000201

AC:

AN:

14938

South Asian (SAS)

AF:

0.00

AC:

AN:

18468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13758

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2272

European-Non Finnish (NFE)

AF:

0.00000356

AC:

AN:

842288

Other (OTH)

AF:

0.0000286

AC:

AN:

34966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.554

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000750

AC:

AN:

146582

Hom.:

Cov.:

AF XY:

0.0000981

AC XY:

AN XY:

71386

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40864

American (AMR)

AF:

0.00

AC:

AN:

14808

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3398

East Asian (EAS)

AF:

0.00199

AC:

AN:

5020

South Asian (SAS)

AF:

0.00

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65974

Other (OTH)

AF:

0.000490

AC:

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0020

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.46

M_CAP

Benign

0.040

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.53

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.64

REVEL

Benign

0.013

Sift

Benign

0.38

Sift4G

Benign

0.56

Polyphen

0.017

Vest4

0.12

MutPred

0.36

Loss of glycosylation at P712 (P = 0.0698)

MVP

0.014

ClinPred

0.097

GERP RS

1.6

Varity_R

0.056

gMVP

0.25

Mutation Taster

=97/3

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over