6-145910588-T-C

Variant names:

• chr6-145910588-T-C
• rs779802630
• NM_001042683.3:c.4375A>G

Variant summary

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

The NM_001042683.3(SHPRH):​c.4375A>G​(p.Ile1459Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,012 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: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SHPRH NM_001042683.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.95
• Publications: 1 publications found

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]

EPM2A-DT (HGNC:48990): (EPM2A divergent transcript)

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=0.26241255).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042683.3. 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
	SHPRH	NM_001042683.3	MANE Select	c.4375A>G	p.Ile1459Val	missense	Exon 25 of 30	NP_001036148.2	Q149N8-1
	SHPRH	NM_001370327.1		c.4375A>G	p.Ile1459Val	missense	Exon 25 of 30	NP_001357256.1	Q149N8-1
	SHPRH	NM_173082.4		c.4387A>G	p.Ile1463Val	missense	Exon 25 of 30	NP_775105.1	Q149N8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHPRH	ENST00000275233.12	TSL:1 MANE Select	c.4375A>G	p.Ile1459Val	missense	Exon 25 of 30	ENSP00000275233.7	Q149N8-1
	SHPRH	ENST00000438092.6	TSL:1	c.4387A>G	p.Ile1463Val	missense	Exon 25 of 30	ENSP00000412797.2	Q149N8-4
	SHPRH	ENST00000433355.6	TSL:1	n.*2978A>G		non_coding_transcript_exon	Exon 24 of 24	ENSP00000408019.2	H7C2W2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000202 AC: 5 AN: 247920 AF XY: 0.0000223

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461012 Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13 AN XY: 726796

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111496

Other (OTH) AF: 0.0000166 AC: 1 AN: 60340

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000828 AC: 1

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	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.57	N
PhyloP100		8.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.20	N
REVEL	Uncertain	0.34
Sift	Benign	0.36	T
Sift4G	Benign	0.50	T
Polyphen		1.0	D
Vest4		0.38
MVP		0.69
MPC		0.64
ClinPred		0.45	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.072
gMVP		0.44
Mutation Taster		=71/29	polymorphism

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: rs779802630; hg19: chr6-146231724;