3-49172865-C-T

Variant names:

• chr3-49172865-C-T
• rs1575547988
• NM_173546.3:c.96C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_173546.3(KLHDC8B):​c.96C>T​(p.His32His) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLHDC8B NM_173546.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.33

Genes affected

KLHDC8B (HGNC:28557): (kelch domain containing 8B) This gene encodes a protein which forms a distinct beta-propeller protein structure of kelch domains allowing for protein-protein interactions. Mutations in this gene have been associated with Hodgkin lymphoma. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 3-49172865-C-T is Benign according to our data. Variant chr3-49172865-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3616904.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.33 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC8B	NM_173546.3	c.96C>T	p.His32His	synonymous_variant	Exon 2 of 6	ENST00000332780.4	NP_775817.1
KLHDC8B	XM_006713015.4	c.96C>T	p.His32His	synonymous_variant	Exon 2 of 6		XP_006713078.1
KLHDC8B	XM_006713016.4	c.96C>T	p.His32His	synonymous_variant	Exon 2 of 6		XP_006713079.1
KLHDC8B	XM_005264938.4	c.96C>T	p.His32His	synonymous_variant	Exon 2 of 6		XP_005264995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHDC8B	ENST00000332780.4	c.96C>T	p.His32His	synonymous_variant	Exon 2 of 6	1	NM_173546.3	ENSP00000327468.2
KLHDC8B	ENST00000476495.2	n.153C>T		non_coding_transcript_exon_variant	Exon 1 of 3	2
KLHDC8B	ENST00000459846.6	n.230+64C>T		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 31, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	9.0
DANN	Benign	0.81

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: rs1575547988; hg19: chr3-49210298;