1-15341792-G-C

Variant names:

• chr1-15341792-G-C
• NM_001391957.1:c.2034G>C
• FHAD1 p.Arg678Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052929.2(FHAD1):​c.1963G>C​(p.Gly655Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G655E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FHAD1 NM_052929.2 missense
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.22956192).

Variant Effect in Transcripts

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

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	5.4
DANN	Benign	0.85
DEOGEN2	Benign	0.00082	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.23	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
PromoterAI		0.0094	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-15668288;