Genetic Variant FAM171A2:p.Pro722Leu (chr17-44354049-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198475.3(FAM171A2):c.2165C>T(p.Pro722Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,149,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

FAM171A2
NM_198475.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23932919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171A2	NM_198475.3 link	c.2165C>T	p.Pro722Leu	missense_variant	Exon 8 of 8	ENST00000293443.12	NP_940877.2	A8MVW0
FAM171A2	XM_017024490.2 link	c.1613C>T	p.Pro538Leu	missense_variant	Exon 6 of 6		XP_016879979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM171A2	ENST00000293443.12 link	c.2165C>T	p.Pro722Leu	missense_variant	Exon 8 of 8	1	NM_198475.3	ENSP00000293443.6		A8MVW0

Frequencies

GnomAD3 genomes

AF:

0.00000678

AC:

AN:

147470

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:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000399

AC:

AN:

1001846

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

AN XY:

471652

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19956

American (AMR)

AF:

0.00

AC:

AN:

5844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10746

East Asian (EAS)

AF:

0.00

AC:

AN:

19292

South Asian (SAS)

AF:

0.00

AC:

AN:

18876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2488

European-Non Finnish (NFE)

AF:

0.00000460

AC:

AN:

869408

Other (OTH)

AF:

0.00

AC:

AN:

37880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000678

AC:

AN:

147470

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

71834

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40930

American (AMR)

AF:

0.00

AC:

AN:

14872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3410

East Asian (EAS)

AF:

0.00

AC:

AN:

5074

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66400

Other (OTH)

AF:

0.00

AC:

AN:

2026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000936

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 06, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2165C>T (p.P722L) alteration is located in exon 8 (coding exon 8) of the FAM171A2 gene. This alteration results from a C to T substitution at nucleotide position 2165, causing the proline (P) at amino acid position 722 to be replaced by a leucine (L). 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

0.18

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0082

Eigen

Benign

0.0054

Eigen_PC

Benign

-0.052

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.60

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

3.5

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.71

REVEL

Benign

0.063

Sift

Uncertain

0.017

Sift4G

Uncertain

0.053

Polyphen

0.97

Vest4

0.13

MutPred

0.36

Loss of glycosylation at P722 (P = 0.0034);

MVP

0.16

ClinPred

0.83

GERP RS

2.8

Varity_R

0.13

gMVP

0.33

Mutation Taster

=78/22

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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17-44354049-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over