Genetic Variant FAM171A2:p.Val536Ile (chr17-44354608-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_198475.3(FAM171A2):c.1606G>A(p.Val536Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000119 in 1,258,068 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FAM171A2
NM_198475.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.55

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.1606G>A	p.Val536Ile	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.1606G>A	p.Val536Ile	missense	Exon 8 of 8	ENSP00000293443.6	A8MVW0
FAM171A2	ENST00000912944.1		c.1642G>A	p.Val548Ile	missense	Exon 9 of 9	ENSP00000583003.1
FAM171A2	ENST00000912945.1		c.1633G>A	p.Val545Ile	missense	Exon 8 of 8	ENSP00000583004.1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150732

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1107336

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

528730

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22818

American (AMR)

AF:

0.00

AC:

AN:

8572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14564

East Asian (EAS)

AF:

0.0000761

AC:

AN:

26264

South Asian (SAS)

AF:

0.0000299

AC:

AN:

33400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23216

Middle Eastern (MID)

AF:

0.000334

AC:

AN:

2998

European-Non Finnish (NFE)

AF:

0.00000859

AC:

AN:

931280

Other (OTH)

AF:

0.0000226

AC:

AN:

44224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

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:

0.0000133

AC:

AN:

150732

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73614

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41302

American (AMR)

AF:

0.00

AC:

AN:

15140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9916

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67630

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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.:

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

0.22

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.79

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.4

PhyloP100

4.5

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.54

REVEL

Benign

0.17

Sift

Uncertain

0.023

Sift4G

Uncertain

0.054

Polyphen

0.98

Vest4

0.16

MutPred

0.64

Gain of catalytic residue at P538 (P = 0.0347)

MVP

0.040

ClinPred

0.96

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.29

Mutation Taster

=92/8

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