8-143249898-G-C

Position:

• chr8-143249898-G-C

Variant summary

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

The NM_173832.6(ZFP41):​c.55G>C​(p.Asp19His) 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: 32)
• Consequence: ZFP41 NM_173832.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00200

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=0.057711124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP41	NM_173832.6	c.55G>C	p.Asp19His	missense_variant	2/3	ENST00000330701.7	NP_776193.3
ZFP41	NM_001271156.3	c.55G>C	p.Asp19His	missense_variant	2/3		NP_001258085.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP41	ENST00000330701.7	c.55G>C	p.Asp19His	missense_variant	2/3	2	NM_173832.6	ENSP00000327427.6
ZFP41	ENST00000520584.6	c.55G>C	p.Asp19His	missense_variant	2/3	1		ENSP00000430465.3
ENSG00000264668	ENST00000522452.2	c.55G>C	p.Asp19His	missense_variant	2/4	1		ENSP00000428966.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 67

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

Sep 26, 2024

The c.55G>C (p.D19H) alteration is located in exon 2 (coding exon 1) of the ZFP41 gene. This alteration results from a G to C substitution at nucleotide position 55, causing the aspartic acid (D) at amino acid position 19 to be replaced by a histidine (H). 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	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.2
DANN	Benign	0.91
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.39	.;T;.
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.22	T
REVEL	Benign	0.032
Sift4G	Benign	0.21	T;T;T
Vest4		0.046
MVP		0.072
MPC		0.074
ClinPred		0.037	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: chr8-144332068;