chr12-109471206-A-G

Variant names:

• chr12-109471206-A-G
• rs2058804
• NM_031954.5:c.4-1478T>C

Variant summary

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

The NM_031954.5(KCTD10):​c.4-1478T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 984,936 control chromosomes in the GnomAD database, including 141,527 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 0.57 (25928 hom., cov: 33)
  • Exomes 𝑓: 0.52 (115599 hom.)
• Consequence: KCTD10 NM_031954.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714
• Publications: 15 publications found

Genes affected

KCTD10 (HGNC:23236): (potassium channel tetramerization domain containing 10) The protein encoded by this gene binds proliferating cell nuclear antigen (PCNA) and may be involved in DNA synthesis and cell proliferation. In addition, the encoded protein may be a tumor suppressor. Several protein-coding and non-protein coding transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

KCTD10 Gene-Disease associations (from GenCC):

• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031954.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD10	NM_031954.5	MANE Select	c.4-1478T>C		intron	N/A	NP_114160.1
	KCTD10	NM_001317395.2		c.4-1478T>C		intron	N/A	NP_001304324.1
	KCTD10	NM_001317399.2		c.4-1478T>C		intron	N/A	NP_001304328.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD10	ENST00000228495.11	TSL:1 MANE Select	c.4-1478T>C		intron	N/A	ENSP00000228495.6
	KCTD10	ENST00000537165.5	TSL:2	n.175T>C		non_coding_transcript_exon	Exon 2 of 7	ENSP00000474497.1
	KCTD10	ENST00000542858.1	TSL:3	c.4-1478T>C		intron	N/A	ENSP00000445129.1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86958 AN: 151994 Hom.: 25881 Cov.: 33

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.586

GnomAD2 exomes AF: 0.500 AC: 11 AN: 22 AF XY: 0.500

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.643

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.525 AC: 437194 AN: 832824 Hom.: 115599 Cov.: 29 AF XY: 0.525 AC XY: 201735 AN XY: 384616

African (AFR) AF: 0.741 AC: 11694 AN: 15784

American (AMR) AF: 0.501 AC: 493 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 2807 AN: 5150

East Asian (EAS) AF: 0.354 AC: 1285 AN: 3632

South Asian (SAS) AF: 0.412 AC: 6782 AN: 16454

European-Finnish (FIN) AF: 0.407 AC: 114 AN: 280

Middle Eastern (MID) AF: 0.586 AC: 950 AN: 1620

European-Non Finnish (NFE) AF: 0.524 AC: 399029 AN: 761634

Other (OTH) AF: 0.515 AC: 14040 AN: 27286

GnomAD4 genome AF: 0.572 AC: 87068 AN: 152112 Hom.: 25928 Cov.: 33 AF XY: 0.563 AC XY: 41859 AN XY: 74350

African (AFR) AF: 0.735 AC: 30489 AN: 41500

American (AMR) AF: 0.503 AC: 7678 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1850 AN: 3468

East Asian (EAS) AF: 0.345 AC: 1786 AN: 5172

South Asian (SAS) AF: 0.406 AC: 1956 AN: 4822

European-Finnish (FIN) AF: 0.464 AC: 4902 AN: 10572

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36475 AN: 67988

Other (OTH) AF: 0.586 AC: 1236 AN: 2108

Alfa AF: 0.559 Hom.: 13735

Bravo AF: 0.586

Asia WGS AF: 0.410 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.92
DANN	Benign	0.34
PhyloP100		-0.71
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: rs2058804; hg19: chr12-109909011; COSMIC: COSV57328279; COSMIC: COSV57328279;