chr17-44353818-G-A

Variant names:

• chr17-44353818-G-A
• rs552337267
• NM_198475.3:c.2396C>T

Variant summary

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

The NM_198475.3(FAM171A2):​c.2396C>T​(p.Ala799Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000347 in 1,423,152 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: FAM171A2 NM_198475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.374
• Publications: 1 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030255318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171A2	NM_198475.3	c.2396C>T	p.Ala799Val	missense_variant	Exon 8 of 8	ENST00000293443.12	NP_940877.2
FAM171A2	XM_017024490.2	c.1844C>T	p.Ala615Val	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	c.2396C>T	p.Ala799Val	missense_variant	Exon 8 of 8	1	NM_198475.3	ENSP00000293443.6

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 281 AN: 150482 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000594

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00145

GnomAD2 exomes AF: 0.000130 AC: 9 AN: 69306 AF XY: 0.000123

Gnomad AFR exome AF: 0.00688

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000167 AC: 213 AN: 1272562 Hom.: 1 Cov.: 30 AF XY: 0.000129 AC XY: 81 AN XY: 627930

African (AFR) AF: 0.00735 AC: 186 AN: 25322

American (AMR) AF: 0.000278 AC: 6 AN: 21566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21572

East Asian (EAS) AF: 0.00 AC: 0 AN: 26258

South Asian (SAS) AF: 0.00 AC: 0 AN: 68914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3866

European-Non Finnish (NFE) AF: 0.00000196 AC: 2 AN: 1022010

Other (OTH) AF: 0.000370 AC: 19 AN: 51414

GnomAD4 genome AF: 0.00187 AC: 281 AN: 150590 Hom.: 0 Cov.: 31 AF XY: 0.00185 AC XY: 136 AN XY: 73590

African (AFR) AF: 0.00650 AC: 268 AN: 41260

American (AMR) AF: 0.000593 AC: 9 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5076

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67390

Other (OTH) AF: 0.00143 AC: 3 AN: 2096

Alfa AF: 0.00185 Hom.: 1

Bravo AF: 0.00193

ExAC AF: 0.000267 AC: 7

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2396C>T (p.A799V) 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 2396, causing the alanine (A) at amino acid position 799 to be replaced by a valine (V). 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	0.086
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.37
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.10
Sift	Benign	0.35	T
Sift4G	Benign	0.29	T
Polyphen		0.0040	B
Vest4		0.020
MutPred		0.44		Loss of relative solvent accessibility (P = 0.0404);
MVP		0.030
ClinPred		0.012	T
GERP RS		-0.71
Varity_R		0.087
gMVP		0.066
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs552337267; hg19: chr17-42431186;