rs1433063901

Variant names:

• chr17-44354005-T-C
• rs1433063901
• NM_198475.3:c.2209A>G

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.2209A>G​(p.Ser737Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000067 in 149,194 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 0.0000067 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM171A2 NM_198475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.925
• 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=0.07164875).

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.2209A>G	p.Ser737Gly	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.2209A>G	p.Ser737Gly	missense	Exon 8 of 8	ENSP00000293443.6	A8MVW0
	FAM171A2	ENST00000912944.1		c.2245A>G	p.Ser749Gly	missense	Exon 9 of 9	ENSP00000583003.1
	FAM171A2	ENST00000912945.1		c.2236A>G	p.Ser746Gly	missense	Exon 8 of 8	ENSP00000583004.1

Frequencies

GnomAD3 genomes AF: 0.00000670 AC: 1 AN: 149194 Hom.: 0 Cov.: 31

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: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000188 AC: 2 AN: 1061532 Hom.: 0 Cov.: 30 AF XY: 0.00000198 AC XY: 1 AN XY: 504372

African (AFR) AF: 0.00 AC: 0 AN: 21382

American (AMR) AF: 0.00 AC: 0 AN: 7252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12720

East Asian (EAS) AF: 0.00 AC: 0 AN: 23124

South Asian (SAS) AF: 0.00 AC: 0 AN: 24504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2724

European-Non Finnish (NFE) AF: 0.00000220 AC: 2 AN: 907202

Other (OTH) AF: 0.00 AC: 0 AN: 41330

GnomAD4 genome AF: 0.00000670 AC: 1 AN: 149194 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 72786

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40982

American (AMR) AF: 0.00 AC: 0 AN: 15012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 5054

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67184

Other (OTH) AF: 0.00 AC: 0 AN: 2058

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	Uncertain	0.36
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	21
DANN	Benign	0.68
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.93
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.033
Sift	Benign	0.66	T
Sift4G	Benign	0.62	T
Polyphen		0.085	B
Vest4		0.040
MutPred		0.34		Loss of phosphorylation at S737 (P = 0.003)
MVP		0.030
ClinPred		0.25	T
GERP RS		3.0
Varity_R		0.16
gMVP		0.25
Mutation Taster		=75/25	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: rs1433063901; hg19: chr17-42431373;