10-7759923-C-G

Position:

• chr10-7759923-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012311.4(KIN):​c.1086G>C​(p.Glu362Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,421,054 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: KIN NM_012311.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.254

Genes affected

KIN (HGNC:6327): (Kin17 DNA and RNA binding protein) The protein encoded by this gene is a nuclear protein that forms intranuclear foci during proliferation and is redistributed in the nucleoplasm during the cell cycle. Short-wave ultraviolet light provokes the relocalization of the protein, suggesting its participation in the cellular response to DNA damage. Originally selected based on protein-binding with RecA antibodies, the mouse protein presents a limited similarity with a functional domain of the bacterial RecA protein, a characteristic shared by this human ortholog. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

KIN (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2633981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIN	NM_012311.4	c.1086G>C	p.Glu362Asp	missense_variant	12/13	ENST00000379562.9	NP_036443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIN	ENST00000379562.9	c.1086G>C	p.Glu362Asp	missense_variant	12/13	1	NM_012311.4	ENSP00000368881.3
KIN	ENST00000463666.5	n.337G>C		non_coding_transcript_exon_variant	5/6	3
KIN	ENST00000471320.5	n.544G>C		non_coding_transcript_exon_variant	4/5	2
KIN	ENST00000498098.1	n.288G>C		non_coding_transcript_exon_variant	4/6	3		ENSP00000473950.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1421054 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 707730

Gnomad4 AFR exome AF: 0.0000316

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.1086G>C (p.E362D) alteration is located in exon 12 (coding exon 12) of the KIN gene. This alteration results from a G to C substitution at nucleotide position 1086, causing the glutamic acid (E) at amino acid position 362 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	0.0052	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	2.9	M
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.18
Sift	Benign	0.30	T
Sift4G	Benign	0.52	T
Polyphen		0.0070	B
Vest4		0.59
MutPred		0.39		Gain of sheet (P = 0.0266);
MVP		0.38
MPC		0.33
ClinPred		0.94	D
GERP RS		0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-7801886;