1-145096920-C-T

Variant names:

• chr1-145096920-C-T
• rs782348436
• NM_207418.3:c.73C>T

Variant summary

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

The NM_207418.3(FAM72D):​c.73C>T​(p.Leu25Phe) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., cov: 13)
  • Exomes 𝑓: 0.000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM72D NM_207418.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07

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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM72D	NM_207418.3	c.73C>T	p.Leu25Phe	missense_variant	Exon 1 of 4	ENST00000400889.3	NP_997301.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM72D	ENST00000400889.3	c.73C>T	p.Leu25Phe	missense_variant	Exon 1 of 4	1	NM_207418.3	ENSP00000383682.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 110682 Hom.: 0 Cov.: 13 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000861

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000109 AC: 12 AN: 1098230 Hom.: 0 Cov.: 15 AF XY: 0.00000545 AC XY: 3 AN XY: 550466

Gnomad4 AFR exome AF: 0.0000472

Gnomad4 AMR exome AF: 0.000265

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000422

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000903 AC: 1 AN: 110682 Hom.: 0 Cov.: 13 AF XY: 0.0000190 AC XY: 1 AN XY: 52682

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000861

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.73C>T (p.L25F) alteration is located in exon 1 (coding exon 1) of the FAM72D gene. This alteration results from a C to T substitution at nucleotide position 73, causing the leucine (L) at amino acid position 25 to be replaced by a phenylalanine (F). 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	0.24
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	27
DEOGEN2	Benign	0.054	T
LIST_S2	Benign	0.82	T
MetaRNN	Uncertain	0.59	D
PROVEAN	Uncertain	-2.8	D
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.025	D
Vest4		0.62
gMVP		0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs782348436; hg19: chr1-143912223;