NM_172193.3:c.96+1681T>C

Variant names:

• chr14-49694971-T-C
• rs10149544
• NM_172193.3:c.96+1681T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172193.3(KLHDC1):​c.96+1681T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 152,286 control chromosomes in the GnomAD database, including 69,769 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.95 (69769 hom., cov: 33)
• Consequence: KLHDC1 NM_172193.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 1 publications found

Genes affected

KLHDC1 (HGNC:19836): (kelch domain containing 1) Enables ubiquitin ligase-substrate adaptor activity. Involved in ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Is active in Cul5-RING ubiquitin ligase complex and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172193.3. 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
	KLHDC1	NM_172193.3	MANE Select	c.96+1681T>C		intron	N/A	NP_751943.1	Q8N7A1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC1	ENST00000359332.7	TSL:1 MANE Select	c.96+1681T>C		intron	N/A	ENSP00000352282.2	Q8N7A1
	KLHDC1	ENST00000555704.5	TSL:1	n.96+1681T>C		intron	N/A	ENSP00000451819.1	G3V4I4
	KLHDC1	ENST00000556392.5	TSL:1	n.96+1681T>C		intron	N/A	ENSP00000450595.1	G3V2D3

Frequencies

GnomAD3 genomes AF: 0.955 AC: 145268 AN: 152168 Hom.: 69722 Cov.: 33

Gnomad AFR AF: 0.844

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.969

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.955 AC: 145372 AN: 152286 Hom.: 69769 Cov.: 33 AF XY: 0.957 AC XY: 71237 AN XY: 74466

African (AFR) AF: 0.844 AC: 35023 AN: 41510

American (AMR) AF: 0.980 AC: 14998 AN: 15304

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5189 AN: 5190

South Asian (SAS) AF: 0.999 AC: 4824 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10616 AN: 10616

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67998 AN: 68046

Other (OTH) AF: 0.970 AC: 2052 AN: 2116

Alfa AF: 0.972 Hom.: 10268

Bravo AF: 0.948

Asia WGS AF: 0.991 AC: 3446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.69
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10149544; hg19: chr14-50161689;