8-143250307-G-C

Position:

• chr8-143250307-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.464G>C​(p.Gly155Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZFP41 NM_173832.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.385

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=0.056489706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP41	NM_173832.6	c.464G>C	p.Gly155Ala	missense_variant	2/3	ENST00000330701.7	NP_776193.3
ZFP41	NM_001271156.3	c.464G>C	p.Gly155Ala	missense_variant	2/3		NP_001258085.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP41	ENST00000330701.7	c.464G>C	p.Gly155Ala	missense_variant	2/3	2	NM_173832.6	ENSP00000327427.6
ZFP41	ENST00000520584.6	c.464G>C	p.Gly155Ala	missense_variant	2/3	1		ENSP00000430465.3
ENSG00000264668	ENST00000522452.2	c.464G>C	p.Gly155Ala	missense_variant	2/4	1		ENSP00000428966.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461722 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

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.: 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

Mar 25, 2024

The c.464G>C (p.G155A) 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 464, causing the glycine (G) at amino acid position 155 to be replaced by an alanine (A). 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	0.19
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.96
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.21	.;T;.
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.40	T
REVEL	Benign	0.063
Sift4G	Benign	0.16	T;T;T
Vest4		0.074
MVP		0.12
MPC		0.095
ClinPred		0.88	D
GERP RS		0.77

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: chr8-144332477;