1-15251811-A-C

Variant names:

• chr1-15251811-A-C
• rs1330660866
• NM_001391957.1:c.27A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001391957.1(FHAD1):​c.27A>C​(p.Glu9Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000029 (0 hom.)
• Consequence: FHAD1 NM_001391957.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.40
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039334267).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001391957.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHAD1	NM_001391957.1	MANE Select	c.27A>C	p.Glu9Asp	missense	Exon 2 of 34	NP_001378886.1	A0A804HIA4
	FHAD1	NM_052929.2		c.27A>C	p.Glu9Asp	missense	Exon 2 of 31	NP_443161.1	B1AJZ9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHAD1	ENST00000688493.1	MANE Select	c.27A>C	p.Glu9Asp	missense	Exon 2 of 34	ENSP00000509124.1	A0A804HIA4
	FHAD1	ENST00000683790.1		c.27A>C	p.Glu9Asp	missense	Exon 2 of 34	ENSP00000506973.1	A0A804HIA4
	FHAD1	ENST00000968213.1		c.27A>C	p.Glu9Asp	missense	Exon 2 of 32	ENSP00000638272.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000631 AC: 1 AN: 158548 AF XY: 0.0000120

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000162

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1399952 Hom.: 0 Cov.: 31 AF XY: 0.00000434 AC XY: 3 AN XY: 690450

African (AFR) AF: 0.00 AC: 0 AN: 31600

American (AMR) AF: 0.00 AC: 0 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1079096

Other (OTH) AF: 0.00 AC: 0 AN: 58164

GnomAD4 genome Cov.: 32

Alfa AF: 0.000111 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.019
DANN	Benign	0.79
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-1.4
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.029
Sift	Benign	0.33	T
Sift4G	Benign	0.45	T
Polyphen		0.0040	B
Vest4		0.072
MutPred		0.32		Loss of sheet (P = 0.0817)
MVP		0.014
ClinPred		0.067	T
GERP RS		-5.5
PromoterAI		0.011	Neutral
Varity_R		0.066
gMVP		0.20
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1330660866; hg19: chr1-15578307;