1-206199826-C-T

Variant names:

• chr1-206199826-C-T
• rs1297676726
• NM_001123168.3:c.211G>A

Variant summary

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

The NM_001123168.3(FAM72A):​c.211G>A​(p.Asp71Asn) 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: 10)
  • Exomes 𝑓: 0.0000049 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM72A NM_001123168.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76

Genes affected

FAM72A (HGNC:24044): (family with sequence similarity 72 member A) Predicted to act upstream of or within negative regulation of brain-derived neurotrophic factor-activated receptor activity and positive regulation of apoptotic process. 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=0.26816624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM72A	NM_001123168.3	c.211G>A	p.Asp71Asn	missense_variant	Exon 2 of 4	ENST00000367128.8	NP_001116640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM72A	ENST00000367128.8	c.211G>A	p.Asp71Asn	missense_variant	Exon 2 of 4	1	NM_001123168.3	ENSP00000356096.3

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000487 AC: 3 AN: 616288 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 330460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000773

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: 0.00

GnomAD4 genome Cov.: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.211G>A (p.D71N) alteration is located in exon 2 (coding exon 2) of the FAM72A gene. This alteration results from a G to A substitution at nucleotide position 211, causing the aspartic acid (D) at amino acid position 71 to be replaced by an asparagine (N). 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	0.32
BayesDel_noAF	Pathogenic	0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T;.;.;.
LIST_S2	Uncertain	0.89	D;D;D;D
MetaRNN	Benign	0.27	T;T;T;T
PROVEAN	Uncertain	-2.4	N;N;N;.
Sift	Benign	0.16	T;T;T;.
Sift4G	Benign	0.25	T;T;T;.
Vest4		0.27
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs1297676726; hg19: chr1-206141504;