8-143249986-C-T

Position:

• chr8-143249986-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173832.6(ZFP41):​c.143C>T​(p.Thr48Ile) 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. 13/16 in silico tools predict 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: 33)
• Consequence: ZFP41 NM_173832.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.714

Genes affected

ZFP41 (HGNC:26786): (ZFP41 zinc finger protein) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000264668 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05185908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP41	NM_173832.6	c.143C>T	p.Thr48Ile	missense_variant	2/3	ENST00000330701.7	NP_776193.3
ZFP41	NM_001271156.3	c.143C>T	p.Thr48Ile	missense_variant	2/3		NP_001258085.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP41	ENST00000330701.7	c.143C>T	p.Thr48Ile	missense_variant	2/3	2	NM_173832.6	ENSP00000327427.6
ZFP41	ENST00000520584.6	c.143C>T	p.Thr48Ile	missense_variant	2/3	1		ENSP00000430465.3
ENSG00000264668	ENST00000522452.2	c.143C>T	p.Thr48Ile	missense_variant	2/4	1		ENSP00000428966.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Oct 19, 2024

The c.143C>T (p.T48I) alteration is located in exon 2 (coding exon 1) of the ZFP41 gene. This alteration results from a C to T substitution at nucleotide position 143, causing the threonine (T) at amino acid position 48 to be replaced by an isoleucine (I). 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	0.16
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.19
DANN	Benign	0.27
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.28	.;T;.
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.25	T
REVEL	Benign	0.0060
Sift4G	Benign	0.26	T;T;T
Vest4		0.074
MVP		0.061
MPC		0.069
ClinPred		0.019	T
GERP RS		-2.8

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: chr8-144332156;