1-15345488-C-G

Position:

• chr1-15345488-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001391957.1(FHAD1):​c.2311C>G​(p.Gln771Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FHAD1 NM_001391957.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

Genes affected

FHAD1 (HGNC:29408): (forkhead associated phosphopeptide binding domain 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08279356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHAD1	NM_001391957.1	c.2311C>G	p.Gln771Glu	missense_variant	18/34	ENST00000688493.1	NP_001378886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHAD1	ENST00000688493.1	c.2311C>G	p.Gln771Glu	missense_variant	18/34		NM_001391957.1	ENSP00000509124	P2

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

May 25, 2022

The c.2245C>G (p.Q749E) alteration is located in exon 17 (coding exon 16) of the FHAD1 gene. This alteration results from a C to G substitution at nucleotide position 2245, causing the glutamine (Q) at amino acid position 749 to be replaced by a glutamic acid (E). 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	0.089
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.8
DANN	Benign	0.97
DEOGEN2	Benign	0.0046	T;T;T;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.77	T;.;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.083	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M;M;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.69	N;N;N;N
REVEL	Benign	0.085
Sift	Uncertain	0.014	D;D;D;D
Sift4G	Benign	0.36	T;T;T;T
Polyphen		0.0050	B;B;.;.
Vest4		0.13
MutPred		0.16		Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);.;.;
MVP		0.048
ClinPred		0.13	T
GERP RS		2.8
Varity_R		0.12
gMVP		0.056

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: chr1-15671984;