1-145099014-A-G

Variant names:

• chr1-145099014-A-G
• rs1553637642
• NM_207418.3:c.179A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_207418.3(FAM72D):​c.179A>G​(p.Tyr60Cys) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 3)
• Consequence: FAM72D NM_207418.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.71

Genes affected

FAM72D (HGNC:33593): (family with sequence similarity 72 member D) Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.8

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM72D	NM_207418.3	c.179A>G	p.Tyr60Cys	missense_variant	Exon 2 of 4	ENST00000400889.3	NP_997301.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM72D	ENST00000400889.3	c.179A>G	p.Tyr60Cys	missense_variant	Exon 2 of 4	1	NM_207418.3	ENSP00000383682.1

Frequencies

GnomAD3 genomes Cov.: 3

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 20, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.179A>G (p.Y60C) alteration is located in exon 2 (coding exon 2) of the FAM72D gene. This alteration results from a A to G substitution at nucleotide position 179, causing the tyrosine (Y) at amino acid position 60 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	28
DEOGEN2	Benign	0.12	T
LIST_S2	Uncertain	0.93	D
MetaRNN	Pathogenic	0.80	D
PROVEAN	Pathogenic	-5.3	D
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Vest4		0.76
gMVP		0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1553637642; hg19: chr1-143910129;