1-15329412-C-A

Variant names:

• chr1-15329412-C-A
• NM_001391957.1:c.1777C>A

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.1777C>A​(p.Gln593Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,050 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: 7.1e-7 (0 hom.)
• Consequence: FHAD1 NM_001391957.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.156
• Publications: 0 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: 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=0.06799939).

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.1777C>A	p.Gln593Lys	missense	Exon 14 of 34	NP_001378886.1	A0A804HIA4
	FHAD1	NM_052929.2		c.1777C>A	p.Gln593Lys	missense	Exon 14 of 31	NP_443161.1	B1AJZ9-1
	FHAD1-AS1	NR_148918.1		n.380G>T		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.1777C>A	p.Gln593Lys	missense	Exon 14 of 34	ENSP00000509124.1	A0A804HIA4
	FHAD1	ENST00000471347.5	TSL:1	n.243C>A		non_coding_transcript_exon	Exon 3 of 24
	FHAD1	ENST00000683790.1		c.1777C>A	p.Gln593Lys	missense	Exon 14 of 34	ENSP00000506973.1	A0A804HIA4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399050 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690024

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35704

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078924

Other (OTH) AF: 0.0000172 AC: 1 AN: 58002

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	0.093
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.16
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Benign	0.18	T
Sift4G	Benign	0.12	T
Polyphen		0.13	B
Vest4		0.15
MutPred		0.26		Gain of methylation at Q593 (P = 0.0185)
MVP		0.16
ClinPred		0.15	T
GERP RS		3.2
Varity_R		0.12
gMVP		0.12
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

hg19: chr1-15655908;