NM_001391957.1:c.2034G>A

Variant names:

• chr1-15341792-G-A
• rs943726679
• NM_001391957.1:c.2034G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001391957.1(FHAD1):​c.2034G>A​(p.Arg678Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FHAD1 NM_001391957.1 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.76
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21671495).
• BP7: Synonymous conserved (PhyloP=1.76 with no splicing effect.

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.2034G>A	p.Arg678Arg	synonymous	Exon 16 of 34	NP_001378886.1	A0A804HIA4
	FHAD1	NM_052929.2		c.1963G>A	p.Gly655Arg	missense	Exon 15 of 31	NP_443161.1	B1AJZ9-1
	FHAD1-AS1	NR_148918.1		n.108+1984C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHAD1	ENST00000688493.1	MANE Select	c.2034G>A	p.Arg678Arg	synonymous	Exon 16 of 34	ENSP00000509124.1	A0A804HIA4
	FHAD1	ENST00000471347.5	TSL:1	n.500G>A		non_coding_transcript_exon	Exon 5 of 24
	FHAD1	ENST00000358897.8	TSL:5	c.1963G>A	p.Gly655Arg	missense	Exon 15 of 31	ENSP00000351770.4	B1AJZ9-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000634 AC: 1 AN: 157642 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000117

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: 0.00000214 AC: 3 AN: 1399426 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690224

African (AFR) AF: 0.00 AC: 0 AN: 31588

American (AMR) AF: 0.00 AC: 0 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078844

Other (OTH) AF: 0.0000172 AC: 1 AN: 58076

GnomAD4 genome Cov.: 33

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	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.7
DANN	Benign	0.85
DEOGEN2	Benign	0.00082	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.088
Sift	Benign	0.32	T
Sift4G	Benign	0.71	T
Polyphen		1.0	D
Vest4		0.16
MutPred		0.20		Gain of MoRF binding (P = 0.0042)
MVP		0.11
ClinPred		0.32	T
GERP RS		3.6
PromoterAI		0.025	Neutral
Varity_R		0.12
gMVP		0.12
Mutation Taster		=99/1	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: rs943726679; hg19: chr1-15668288;