chr6-145924812-C-T

Position:

• chr6-145924812-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001042683.3(SHPRH):​c.3329G>A​(p.Cys1110Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SHPRH NM_001042683.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51

Genes affected

SHPRH (HGNC:19336): (SNF2 histone linker PHD RING helicase) SHPRH is a ubiquitously expressed protein that contains motifs characteristics of several DNA repair proteins, transcription factors, and helicases. SHPRH is a functional homolog of S. cerevisiae RAD5 (Unk et al., 2006 [PubMed 17108083]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05440715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHPRH	NM_001042683.3	c.3329G>A	p.Cys1110Tyr	missense_variant	17/30	ENST00000275233.12	NP_001036148.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHPRH	ENST00000275233.12	c.3329G>A	p.Cys1110Tyr	missense_variant	17/30	1	NM_001042683.3	ENSP00000275233	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

The c.3329G>A (p.C1110Y) alteration is located in exon 17 (coding exon 16) of the SHPRH gene. This alteration results from a G to A substitution at nucleotide position 3329, causing the cysteine (C) at amino acid position 1110 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.48
DEOGEN2	Benign	0.014	T;.;.;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.88	.;D;D;D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.054	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.67	N;.;.;N
MutationTaster	Benign	0.60	D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	1.3	N;N;.;N
REVEL	Benign	0.12
Sift	Benign	0.97	T;T;.;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;B;.;B
Vest4		0.18
MutPred		0.45		Gain of solvent accessibility (P = 4e-04);.;.;Gain of solvent accessibility (P = 4e-04);
MVP		0.59
MPC		0.93
ClinPred		0.62	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.40

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-146245948;