chr16-67663693-T-A

Position:

• chr16-67663693-T-A

Variant summary

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

The NM_032140.3(ENKD1):​c.707A>T​(p.His236Leu) variant causes a missense 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ENKD1 NM_032140.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12

Genes affected

ENKD1 (HGNC:25246): (enkurin domain containing 1) Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ENKD1 (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=0.07476747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENKD1	NM_032140.3	c.707A>T	p.His236Leu	missense_variant	5/7	ENST00000243878.9	NP_115516.1
ENKD1	XM_024450469.2	c.581A>T	p.His194Leu	missense_variant	4/6		XP_024306237.1
ENKD1	XM_024450470.2	c.707A>T	p.His236Leu	missense_variant	5/6		XP_024306238.1
ENKD1	NR_138150.2	n.842A>T		non_coding_transcript_exon_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENKD1	ENST00000243878.9	c.707A>T	p.His236Leu	missense_variant	5/7	1	NM_032140.3	ENSP00000243878.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

May 16, 2023

The c.707A>T (p.H236L) alteration is located in exon 5 (coding exon 5) of the ENKD1 gene. This alteration results from a A to T substitution at nucleotide position 707, causing the histidine (H) at amino acid position 236 to be replaced by a leucine (L). 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	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.056
Sift	Benign	0.25	T
Sift4G	Benign	0.47	T
Polyphen		0.029	B
Vest4		0.26
MutPred		0.19		Loss of loop (P = 0.1242);
MVP		0.44
MPC		0.28
ClinPred		0.14	T
GERP RS		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.074
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-67697596;