rs34044330

Variant names:

• chr17-41724751-C-A
• rs34044330
• NM_177977.3:c.1810G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41724751-C-A
• chr17-41724751-C-G
• chr17-41724751-C-T

Variant summary

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

The NM_177977.3(HAP1):​c.1810G>T​(p.Gly604Trp) 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. 14/22 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. G604R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HAP1 NM_177977.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 0 publications found

Genes affected

HAP1 (HGNC:4812): (huntingtin associated protein 1) Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with huntingtin, with two cytoskeletal proteins (dynactin and pericentriolar autoantigen protein 1), and with a hepatocyte growth factor-regulated tyrosine kinase substrate. The interactions with cytoskeletal proteins and a kinase substrate suggest a role for this protein in vesicular trafficking or organelle transport. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

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=0.12492144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAP1	NM_177977.3	c.1810G>T	p.Gly604Trp	missense_variant	Exon 11 of 11	ENST00000347901.9	NP_817084.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAP1	ENST00000347901.9	c.1810G>T	p.Gly604Trp	missense_variant	Exon 11 of 11	1	NM_177977.3	ENSP00000334002.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	.;.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.55	T;T;T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	.;.;.;L
PhyloP100		-0.090
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.7	D;D;D;D
REVEL	Benign	0.034
Sift	Uncertain	0.020	D;D;D;D
Sift4G	Uncertain	0.039	D;D;D;D
Polyphen		0.65	P;B;P;B
Vest4		0.25
MutPred		0.29		.;.;.;Loss of disorder (P = 0.004);
MVP		0.35
MPC		0.56
ClinPred		0.75	D
GERP RS		-2.4
PromoterAI		0.0072	Neutral
Varity_R		0.039
gMVP		0.017

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: rs34044330; hg19: chr17-39881003;