NM_152643.8:c.171C>G

Variant names:

• chr10-133167449-C-G
• rs140318541
• NM_152643.8:c.171C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_152643.8(KNDC1):​c.171C>G​(p.Ala57Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,453,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A57A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: KNDC1 NM_152643.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51
• Publications: 1 publications found

Genes affected

KNDC1 (HGNC:29374): (kinase non-catalytic C-lobe domain containing 1) The protein encoded by this gene is a Ras guanine nucleotide exchange factor that appears to negatively regulate dendritic growth in the brain. Knockdown of this gene in senescent umbilical vein endothelial cells partially reversed the senescence, showing that this gene could potentially be targeted by anti-aging therapies. [provided by RefSeq, Dec 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-2.51 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152643.8. 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
	KNDC1	NM_152643.8	MANE Select	c.171C>G	p.Ala57Ala	synonymous	Exon 2 of 30	NP_689856.6
	KNDC1	NM_001347864.2		c.171C>G	p.Ala57Ala	synonymous	Exon 2 of 3	NP_001334793.1	A0A804HIZ4
	KNDC1	NM_001347865.2		c.171C>G	p.Ala57Ala	synonymous	Exon 2 of 4	NP_001334794.1	A0A804HID6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KNDC1	ENST00000304613.8	TSL:1 MANE Select	c.171C>G	p.Ala57Ala	synonymous	Exon 2 of 30	ENSP00000304437.3	Q76NI1-1
	KNDC1	ENST00000368571.3	TSL:1	c.171C>G	p.Ala57Ala	synonymous	Exon 2 of 17	ENSP00000357560.3	Q76NI1-4
	KNDC1	ENST00000946348.1		c.171C>G	p.Ala57Ala	synonymous	Exon 2 of 31	ENSP00000616407.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000860 AC: 2 AN: 232690 AF XY: 0.0000158

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000213 AC: 31 AN: 1453786 Hom.: 0 Cov.: 32 AF XY: 0.0000221 AC XY: 16 AN XY: 722444

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 43796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25848

East Asian (EAS) AF: 0.00 AC: 0 AN: 39378

South Asian (SAS) AF: 0.00 AC: 0 AN: 84376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51678

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1109472

Other (OTH) AF: 0.00 AC: 0 AN: 60056

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.48
DANN	Benign	0.71
PhyloP100		-2.5

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: rs140318541; hg19: chr10-134980953;