1-15289526-C-T

Variant names:

• chr1-15289526-C-T
• rs563528811
• NM_001391957.1:c.428C>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.428C>T​(p.Pro143Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000322 in 1,551,896 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: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FHAD1 NM_001391957.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.66
• Publications: 0 publications found

Genes affected

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

LOC124903853 (HGNC:):

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=0.08244184).

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.428C>T	p.Pro143Leu	missense	Exon 4 of 34	NP_001378886.1	A0A804HIA4
	FHAD1	NM_052929.2		c.428C>T	p.Pro143Leu	missense	Exon 4 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.428C>T	p.Pro143Leu	missense	Exon 4 of 34	ENSP00000509124.1	A0A804HIA4
	FHAD1	ENST00000683790.1		c.428C>T	p.Pro143Leu	missense	Exon 4 of 34	ENSP00000506973.1	A0A804HIA4
	FHAD1	ENST00000968213.1		c.428C>T	p.Pro143Leu	missense	Exon 4 of 32	ENSP00000638272.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399550 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 690284

African (AFR) AF: 0.00 AC: 0 AN: 31598

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: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1079008

Other (OTH) AF: 0.00 AC: 0 AN: 58036

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74496

African (AFR) AF: 0.0000240 AC: 1 AN: 41582

American (AMR) AF: 0.0000653 AC: 1 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.55
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.7
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.056
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.90	P
Vest4		0.23
MutPred		0.25		Gain of MoRF binding (P = 0.0538)
MVP		0.095
ClinPred		0.33	T
GERP RS		3.0
Varity_R		0.086
gMVP		0.43
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs563528811; hg19: chr1-15616022;