15-59460021-A-T

Position:

• chr15-59460021-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152450.3(FAM81A):​c.109A>T​(p.Ile37Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM81A NM_152450.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58

Genes affected

FAM81A (HGNC:28379): (family with sequence similarity 81 member A)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM81A	NM_152450.3	c.109A>T	p.Ile37Phe	missense_variant	3/9	ENST00000288228.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM81A	ENST00000288228.10	c.109A>T	p.Ile37Phe	missense_variant	3/9	1	NM_152450.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2022

The c.109A>T (p.I37F) alteration is located in exon 3 (coding exon 2) of the FAM81A gene. This alteration results from a A to T substitution at nucleotide position 109, causing the isoleucine (I) at amino acid position 37 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	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;.;T;T;T;.;T;.;.;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.86	D;D;D;D;D;D;D;.;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.47	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.6	D;N;N;D;D;N;D;D;D;D
Sift	Uncertain	0.012	D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.050	T;T;D;D;D;D;T;T;D;T
Polyphen		1.0	.;.;D;.;.;.;.;.;.;.
Vest4		0.84
MutPred		0.42		Loss of stability (P = 0.0595);Loss of stability (P = 0.0595);Loss of stability (P = 0.0595);Loss of stability (P = 0.0595);Loss of stability (P = 0.0595);.;.;Loss of stability (P = 0.0595);Loss of stability (P = 0.0595);Loss of stability (P = 0.0595);
MVP		0.31
MPC		1.7
ClinPred		0.92	D
GERP RS		5.6
Varity_R		0.29
gMVP		0.97

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-59752220;