1-15251804-G-C

Position:

• chr1-15251804-G-C

Variant summary

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

The NM_001391957.1(FHAD1):​c.20G>C​(p.Ser7Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000714 in 1,399,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FHAD1 NM_001391957.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.51

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=0.20712903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHAD1	NM_001391957.1	c.20G>C	p.Ser7Thr	missense_variant	2/34	ENST00000688493.1	NP_001378886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHAD1	ENST00000688493.1	c.20G>C	p.Ser7Thr	missense_variant	2/34		NM_001391957.1	ENSP00000509124	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399852 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690416

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

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

Feb 06, 2023

The c.20G>C (p.S7T) alteration is located in exon 2 (coding exon 1) of the FHAD1 gene. This alteration results from a G to C substitution at nucleotide position 20, causing the serine (S) at amino acid position 7 to be replaced by a threonine (T). 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	0.30
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0034	T;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.59	T;.
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	0.98	N;N;N;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.95	N;N
REVEL	Benign	0.18
Sift	Benign	0.038	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.12
MutPred		0.37		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.12
ClinPred		0.81	D
GERP RS		5.0
Varity_R		0.20
gMVP		0.36

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: chr1-15578300;