rs1447824351

Variant names:

• chr17-44353971-G-A
• rs1447824351
• NM_198475.3:c.2243C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-44353971-G-A
• chr17-44353971-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198475.3(FAM171A2):​c.2243C>T​(p.Ser748Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000175 in 1,141,944 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: FAM171A2 NM_198475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.02
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39439908).

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.2243C>T	p.Ser748Leu	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.2243C>T	p.Ser748Leu	missense	Exon 8 of 8	ENSP00000293443.6	A8MVW0
	FAM171A2	ENST00000912944.1		c.2279C>T	p.Ser760Leu	missense	Exon 9 of 9	ENSP00000583003.1
	FAM171A2	ENST00000912945.1		c.2270C>T	p.Ser757Leu	missense	Exon 8 of 8	ENSP00000583004.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000175 AC: 2 AN: 1141944 Hom.: 0 Cov.: 30 AF XY: 0.00000180 AC XY: 1 AN XY: 554144

African (AFR) AF: 0.0000445 AC: 1 AN: 22458

American (AMR) AF: 0.00 AC: 0 AN: 9464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14694

East Asian (EAS) AF: 0.00 AC: 0 AN: 24836

South Asian (SAS) AF: 0.0000250 AC: 1 AN: 39948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3022

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 956534

Other (OTH) AF: 0.00 AC: 0 AN: 45284

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	Pathogenic	0.64
BayesDel_addAF	Benign	-0.0078	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	D
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		9.0
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.21
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.35		Loss of phosphorylation at S748 (P = 0.0284)
MVP		0.18
ClinPred		0.95	D
GERP RS		1.5
Varity_R		0.27
gMVP		0.43

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: rs1447824351; hg19: chr17-42431339;