chr17-44354515-C-T

Variant names:

• chr17-44354515-C-T
• rs1294823709
• NM_198475.3:c.1699G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198475.3(FAM171A2):​c.1699G>A​(p.Gly567Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000203 in 147,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM171A2 NM_198475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19
• Publications: 0 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: 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=0.16424501).

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.1699G>A	p.Gly567Ser	missense	Exon 8 of 8	NP_940877.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM171A2	ENST00000293443.12	TSL:1 MANE Select	c.1699G>A	p.Gly567Ser	missense	Exon 8 of 8	ENSP00000293443.6	A8MVW0
	FAM171A2	ENST00000912944.1		c.1735G>A	p.Gly579Ser	missense	Exon 9 of 9	ENSP00000583003.1
	FAM171A2	ENST00000912945.1		c.1726G>A	p.Gly576Ser	missense	Exon 8 of 8	ENSP00000583004.1

Frequencies

GnomAD3 genomes AF: 0.0000203 AC: 3 AN: 147834 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000201

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000406 AC: 4 AN: 986026 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 464364

African (AFR) AF: 0.00 AC: 0 AN: 19636

American (AMR) AF: 0.000544 AC: 3 AN: 5512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9972

East Asian (EAS) AF: 0.00 AC: 0 AN: 17362

South Asian (SAS) AF: 0.00 AC: 0 AN: 18636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2412

European-Non Finnish (NFE) AF: 0.00000116 AC: 1 AN: 858458

Other (OTH) AF: 0.00 AC: 0 AN: 36940

GnomAD4 genome AF: 0.0000203 AC: 3 AN: 147932 Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1 AN XY: 72100

African (AFR) AF: 0.00 AC: 0 AN: 41056

American (AMR) AF: 0.000201 AC: 3 AN: 14948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3398

East Asian (EAS) AF: 0.00 AC: 0 AN: 5078

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66402

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000567

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.72	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.2
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.061
Sift	Benign	0.74	T
Sift4G	Benign	0.74	T
Polyphen		0.96	D
Vest4		0.058
MutPred		0.33		Gain of glycosylation at G567 (P = 4e-04)
MVP		0.040
ClinPred		0.35	T
GERP RS		3.1
Varity_R		0.042
gMVP		0.38
Mutation Taster		=89/11	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: rs1294823709; hg19: chr17-42431883;