chr1-145103079-C-A

Variant names:

• chr1-145103079-C-A
• rs1553638146
• NM_207418.3:c.303C>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_207418.3(FAM72D):​c.303C>A​(p.Phe101Leu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 17)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM72D NM_207418.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67

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 Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.36138353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM72D	NM_207418.3	c.303C>A	p.Phe101Leu	missense_variant	Exon 3 of 4	ENST00000400889.3	NP_997301.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM72D	ENST00000400889.3	c.303C>A	p.Phe101Leu	missense_variant	Exon 3 of 4	1	NM_207418.3	ENSP00000383682.1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.87e-7 AC: 1 AN: 1456238 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724408

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 17

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.303C>A (p.F101L) alteration is located in exon 3 (coding exon 3) of the FAM72D gene. This alteration results from a C to A substitution at nucleotide position 303, causing the phenylalanine (F) at amino acid position 101 to be replaced by a leucine (L). 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	Pathogenic	0.63
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DEOGEN2	Benign	0.022	T
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.36	T
PROVEAN	Benign	-2.2	N
Sift	Benign	0.29	T
Sift4G	Benign	0.22	T
Vest4		0.44
gMVP		0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1553638146; hg19: chr1-143906064;