8-144099920-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_030974.4(SHARPIN):c.517+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000615 in 1,610,136 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (3 hom.)
• Consequence: SHARPIN NM_030974.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.385

Genes affected

SHARPIN (HGNC:25321): (SHANK associated RH domain interactor) Enables polyubiquitin modification-dependent protein binding activity. Involved in protein linear polyubiquitination and regulation of signal transduction. Located in cytosol. Part of LUBAC complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-144099920-C-A is Benign according to our data. Variant chr8-144099920-C-A is described in ClinVar as [Benign]. Clinvar id is 711023.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHARPIN	NM_030974.4	c.517+9G>T		intron_variant		ENST00000398712.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHARPIN	ENST00000398712.7	c.517+9G>T		intron_variant		1	NM_030974.4	P1

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 470 AN: 151888 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000881 AC: 212 AN: 240588 Hom.: 2 AF XY: 0.000718 AC XY: 94 AN XY: 130952

Gnomad AFR exome AF: 0.0126

Gnomad AMR exome AF: 0.000266

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000999

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000744

Gnomad OTH exome AF: 0.000512

GnomAD4 exome AF: 0.000355 AC: 517 AN: 1458136 Hom.: 3 Cov.: 51 AF XY: 0.000314 AC XY: 228 AN XY: 725128

Gnomad4 AFR exome AF: 0.0127

Gnomad4 AMR exome AF: 0.000474

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000466

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.000582

GnomAD4 genome AF: 0.00311 AC: 473 AN: 152000 Hom.: 6 Cov.: 32 AF XY: 0.00320 AC XY: 238 AN XY: 74310

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000883

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000156 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 02, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.8
Dann	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs199932176; hg19: chr8-145154823;