17-44354049-G-T

Variant names:

• chr17-44354049-G-T
• rs2048406063
• NM_198475.3:c.2165C>A

Variant summary

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

The NM_198475.3(FAM171A2):​c.2165C>A​(p.Pro722Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000002 in 1,001,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P722L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: FAM171A2 NM_198475.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.52
• 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=0.2765832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171A2	NM_198475.3	c.2165C>A	p.Pro722Gln	missense_variant	Exon 8 of 8	ENST00000293443.12	NP_940877.2
FAM171A2	XM_017024490.2	c.1613C>A	p.Pro538Gln	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.2165C>A	p.Pro722Gln	missense_variant	Exon 8 of 8	1	NM_198475.3	ENSP00000293443.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000200 AC: 2 AN: 1001844 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 471650

African (AFR) AF: 0.00 AC: 0 AN: 19956

American (AMR) AF: 0.00 AC: 0 AN: 5844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10746

East Asian (EAS) AF: 0.00 AC: 0 AN: 19292

South Asian (SAS) AF: 0.0000530 AC: 1 AN: 18874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2488

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 869408

Other (OTH) AF: 0.0000264 AC: 1 AN: 37880

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0030	T
Eigen	Benign	0.091
Eigen_PC	Benign	0.0084
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.5
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.32	N
REVEL	Benign	0.10
Sift	Benign	0.049	D
Sift4G	Benign	0.074	T
Polyphen		0.98	D
Vest4		0.26
MutPred		0.32		Loss of glycosylation at P722 (P = 0.0034);
MVP		0.10
ClinPred		0.81	D
GERP RS		2.8
Varity_R		0.092
gMVP		0.30

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: rs2048406063; hg19: chr17-42431417;