1-15328368-C-T

Variant names:

• chr1-15328368-C-T
• rs1163164780
• NM_001391957.1:c.1649C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001391957.1(FHAD1):​c.1649C>T​(p.Ser550Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.000022 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FHAD1 NM_001391957.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.408
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06836179).

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.1649C>T	p.Ser550Phe	missense	Exon 13 of 34	NP_001378886.1	A0A804HIA4
	FHAD1	NM_052929.2		c.1649C>T	p.Ser550Phe	missense	Exon 13 of 31	NP_443161.1	B1AJZ9-1
	FHAD1-AS1	NR_148918.1		n.1424G>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.1649C>T	p.Ser550Phe	missense	Exon 13 of 34	ENSP00000509124.1	A0A804HIA4
	FHAD1	ENST00000471347.5	TSL:1	n.115C>T		non_coding_transcript_exon	Exon 2 of 24
	FHAD1	ENST00000683790.1		c.1649C>T	p.Ser550Phe	missense	Exon 13 of 34	ENSP00000506973.1	A0A804HIA4

Frequencies

GnomAD3 genomes AF: 0.0000221 AC: 3 AN: 136022 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000140 AC: 19 AN: 1357154 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 9 AN XY: 669266

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000331 AC: 1 AN: 30210

American (AMR) AF: 0.00 AC: 0 AN: 32746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24234

East Asian (EAS) AF: 0.00 AC: 0 AN: 33680

South Asian (SAS) AF: 0.0000136 AC: 1 AN: 73522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5562

European-Non Finnish (NFE) AF: 0.0000142 AC: 15 AN: 1053506

Other (OTH) AF: 0.0000359 AC: 2 AN: 55744

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000221 AC: 3 AN: 136022 Hom.: 0 Cov.: 30 AF XY: 0.0000150 AC XY: 1 AN XY: 66494

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000555 AC: 2 AN: 36014

American (AMR) AF: 0.00 AC: 0 AN: 13568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3080

East Asian (EAS) AF: 0.00 AC: 0 AN: 4812

South Asian (SAS) AF: 0.00 AC: 0 AN: 4106

European-Finnish (FIN) AF: 0.000103 AC: 1 AN: 9698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61802

Other (OTH) AF: 0.00 AC: 0 AN: 1788

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0160444), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 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	0.15
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	12
DANN	Benign	0.83
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.41
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.24
Sift	Benign	0.15	T
Sift4G	Uncertain	0.010	D
Polyphen		0.0020	B
Vest4		0.17
MutPred		0.12		Gain of methylation at K551 (P = 0.0264)
MVP		0.061
ClinPred		0.31	T
GERP RS		-2.6
Varity_R		0.074
gMVP		0.14
Mutation Taster		=91/9	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: rs1163164780; hg19: chr1-15654864;