chr1-15327116-C-T

Variant names:

• chr1-15327116-C-T
• rs1487960230
• NM_001391957.1:c.1531C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001391957.1(FHAD1):​c.1531C>T​(p.Arg511Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,399,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000093 (0 hom.)
• Consequence: FHAD1 NM_001391957.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79
• Publications: 1 publications found

Genes affected

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

FHAD1-AS1 (HGNC:41241): (FHAD1 antisense RNA 1)

EFHD2-AS1 (HGNC:55801): (EFHD2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20314535).

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.1531C>T	p.Arg511Trp	missense	Exon 12 of 34	NP_001378886.1	A0A804HIA4
	FHAD1	NM_052929.2		c.1531C>T	p.Arg511Trp	missense	Exon 12 of 31	NP_443161.1	B1AJZ9-1
	FHAD1-AS1	NR_148918.1		n.2676G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHAD1	ENST00000688493.1	MANE Select	c.1531C>T	p.Arg511Trp	missense	Exon 12 of 34	ENSP00000509124.1	A0A804HIA4
	FHAD1	ENST00000683790.1		c.1531C>T	p.Arg511Trp	missense	Exon 12 of 34	ENSP00000506973.1	A0A804HIA4
	FHAD1	ENST00000968213.1		c.1531C>T	p.Arg511Trp	missense	Exon 12 of 32	ENSP00000638272.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000129 AC: 2 AN: 155588 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000407

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000929 AC: 13 AN: 1399072 Hom.: 0 Cov.: 31 AF XY: 0.00000725 AC XY: 5 AN XY: 690044

African (AFR) AF: 0.0000633 AC: 2 AN: 31596

American (AMR) AF: 0.0000280 AC: 1 AN: 35676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49182

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5698

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1078824

Other (OTH) AF: 0.0000690 AC: 4 AN: 58000

GnomAD4 genome Cov.: 32

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	0.085
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.8
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.4	N
REVEL	Benign	0.27
Sift	Benign	0.030	D
Sift4G	Uncertain	0.016	D
Polyphen		0.91	P
Vest4		0.12
MutPred		0.37		Loss of disorder (P = 0.0079)
MVP		0.32
ClinPred		0.69	D
GERP RS		5.4
Varity_R		0.087
gMVP		0.087
Mutation Taster		=82/18	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: rs1487960230; hg19: chr1-15653612;