Genetic Variant NM_198475.3:c.1691C>T (chr17-44354523-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_198475.3(FAM171A2):c.1691C>T(p.Pro564Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000078 in 1,153,792 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 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

FAM171A2
NM_198475.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.617

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18006894).

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.1691C>T	p.Pro564Leu	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.1691C>T	p.Pro564Leu	missense	Exon 8 of 8	ENSP00000293443.6	A8MVW0
FAM171A2	ENST00000912944.1		c.1727C>T	p.Pro576Leu	missense	Exon 9 of 9	ENSP00000583003.1
FAM171A2	ENST00000912945.1		c.1718C>T	p.Pro573Leu	missense	Exon 8 of 8	ENSP00000583004.1

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

147952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000488

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000696

AC:

AN:

1005840

Hom.:

Cov.:

AF XY:

0.00000844

AC XY:

AN XY:

474212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20178

American (AMR)

AF:

0.00

AC:

AN:

6122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10754

East Asian (EAS)

AF:

0.000304

AC:

AN:

19718

South Asian (SAS)

AF:

0.00

AC:

AN:

18848

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2482

European-Non Finnish (NFE)

AF:

0.00000115

AC:

AN:

871138

Other (OTH)

AF:

0.00

AC:

AN:

38246

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:

0.0000135

AC:

AN:

147952

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

72084

show subpopulations

African (AFR)

AF:

0.0000488

AC:

AN:

40968

American (AMR)

AF:

0.00

AC:

AN:

14934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3400

East Asian (EAS)

AF:

0.00

AC:

AN:

5096

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9028

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66442

Other (OTH)

AF:

0.00

AC:

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000491

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

0.069

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0034

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.52

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

0.62

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.1

REVEL

Benign

0.014

Sift

Benign

0.31

Sift4G

Benign

0.23

Polyphen

0.34

Vest4

0.14

MutPred

0.46

Loss of glycosylation at P564 (P = 0.0258)

MVP

0.061

ClinPred

0.096

GERP RS

3.1

Varity_R

0.036

gMVP

0.30

Mutation Taster

=91/9

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