1-15289642-C-G

Variant names:

• chr1-15289642-C-G
• rs548188217
• NM_001391957.1:c.544C>G

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.544C>G​(p.Arg182Gly) 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 1,397,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R182C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: FHAD1 NM_001391957.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.01
• Publications: 1 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=0.10444614).

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.544C>G	p.Arg182Gly	missense	Exon 4 of 34	NP_001378886.1	A0A804HIA4
	FHAD1	NM_052929.2		c.544C>G	p.Arg182Gly	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.544C>G	p.Arg182Gly	missense	Exon 4 of 34	ENSP00000509124.1	A0A804HIA4
	FHAD1	ENST00000683790.1		c.544C>G	p.Arg182Gly	missense	Exon 4 of 34	ENSP00000506973.1	A0A804HIA4
	FHAD1	ENST00000968213.1		c.544C>G	p.Arg182Gly	missense	Exon 4 of 32	ENSP00000638272.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1397784 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 689050

African (AFR) AF: 0.00 AC: 0 AN: 31572

American (AMR) AF: 0.00 AC: 0 AN: 35670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25166

East Asian (EAS) AF: 0.00 AC: 0 AN: 35684

South Asian (SAS) AF: 0.00 AC: 0 AN: 79186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1077674

Other (OTH) AF: 0.00 AC: 0 AN: 57940

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.1
DANN	Benign	0.93
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.0
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.094
Sift	Benign	0.35	T
Sift4G	Benign	0.25	T
Polyphen		0.15	B
Vest4		0.061
MutPred		0.35		Loss of MoRF binding (P = 0.031)
MVP		0.25
ClinPred		0.20	T
GERP RS		3.8
Varity_R		0.054
gMVP		0.21
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: rs548188217; hg19: chr1-15616138;