NM_198475.3:c.1703C>G

Variant names:

• chr17-44354511-G-C
• rs2048410576
• NM_198475.3:c.1703C>G

Variant summary

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

The NM_198475.3(FAM171A2):​c.1703C>G​(p.Thr568Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000615 in 975,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000061 (0 hom.)
• Consequence: FAM171A2 NM_198475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06726718).

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.1703C>G	p.Thr568Arg	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.1703C>G	p.Thr568Arg	missense	Exon 8 of 8	ENSP00000293443.6	A8MVW0
	FAM171A2	ENST00000912944.1		c.1739C>G	p.Thr580Arg	missense	Exon 9 of 9	ENSP00000583003.1
	FAM171A2	ENST00000912945.1		c.1730C>G	p.Thr577Arg	missense	Exon 8 of 8	ENSP00000583004.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000615 AC: 6 AN: 975634 Hom.: 0 Cov.: 31 AF XY: 0.00000436 AC XY: 2 AN XY: 459214

African (AFR) AF: 0.00 AC: 0 AN: 19328

American (AMR) AF: 0.00 AC: 0 AN: 5234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9542

East Asian (EAS) AF: 0.00 AC: 0 AN: 16126

South Asian (SAS) AF: 0.000323 AC: 6 AN: 18568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2354

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 852004

Other (OTH) AF: 0.00 AC: 0 AN: 36270

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.82
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.33	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.5
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.091
Sift	Benign	0.41	T
Sift4G	Benign	0.45	T
Polyphen		0.0040	B
Vest4		0.077
MutPred		0.35		Loss of glycosylation at T568 (P = 0.0046)
MVP		0.030
ClinPred		0.086	T
GERP RS		3.5
Varity_R		0.14
gMVP		0.27
Mutation Taster		=95/5	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: rs2048410576; hg19: chr17-42431879;