14-73904932-A-T

Position:

• chr14-73904932-A-T

Variant summary

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

The ENST00000555044.6(ZNF410):​c.762A>T​(p.Glu254Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E254K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF410 ENST00000555044.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47

Genes affected

ZNF410 (HGNC:20144): (zinc finger protein 410) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF410 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF410	NM_021188.3	c.762A>T	p.Glu254Asp	missense_variant	7/12	ENST00000555044.6	NP_067011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF410	ENST00000555044.6	c.762A>T	p.Glu254Asp	missense_variant	7/12	1	NM_021188.3	ENSP00000451763.2
ENSG00000258653	ENST00000556551.2	n.*1021A>T		non_coding_transcript_exon_variant	16/22	2		ENSP00000451484.1
ENSG00000258653	ENST00000556551.2	n.*1021A>T		3_prime_UTR_variant	16/22	2		ENSP00000451484.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Nov 10, 2022

The c.813A>T (p.E271D) alteration is located in exon 8 (coding exon 7) of the ZNF410 gene. This alteration results from a A to T substitution at nucleotide position 813, causing the glutamic acid (E) at amino acid position 271 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	Benign	0.27
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	.;.;.;T;.;.;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D;.;D;D;D;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.27	T;T;T;T;T;T;T
MetaSVM	Benign	-0.58	T
MutationTaster	Benign	1.0	D;D;D;D;D;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.1	N;N;N;N;N;.;.
REVEL	Benign	0.041
Sift	Uncertain	0.024	D;D;D;D;D;.;.
Sift4G	Uncertain	0.021	D;D;D;D;D;D;.
Polyphen		0.66, 0.71	.;P;.;P;.;.;.
Vest4		0.30
MutPred		0.38		.;Loss of ubiquitination at K258 (P = 0.1037);.;Loss of ubiquitination at K258 (P = 0.1037);.;.;.;
MVP		0.29
MPC		0.62
ClinPred		0.80	D
GERP RS		3.3
Varity_R		0.38
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.36		Position offset: -1

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: chr14-74371635;