rs104894955

chrX-47449438-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001324144.2(ZNF41):c.332C>T(p.Pro111Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,207,428 control chromosomes in the GnomAD database, including 1 homozygotes. There are 539 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., 22 hem., cov: 22)
  • Exomes 𝑓: 0.0016 (1 hom. 517 hem.)
• Consequence: ZNF41 NM_001324144.2 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts U:1 B:2
• Conservation: PhyloP100: 1.48

Genes affected

ZNF41 (HGNC:13107): (zinc finger protein 41) This gene encodes a protein that contains KRAB-A and KRAB-B domains multiple zinc finger DNA binding motifs and finger linking regions characteristic of the Kruppel family. An initial study suggested that this gene may be associated with X-linked cognitive disability, but a later study has called this finding into question (PMID:23871722).[provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019093096).
• BP6: Variant X-47449438-G-A is Benign according to our data. Variant chrX-47449438-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 9760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47449438-G-A is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd at 22 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF41	NM_001324144.2	c.332C>T	p.Pro111Leu	missense_variant	5/5	ENST00000684689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF41	ENST00000684689.1	c.332C>T	p.Pro111Leu	missense_variant	5/5		NM_001324144.2	P1

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 70 AN: 110869 Hom.: 0 Cov.: 22 AF XY: 0.000664 AC XY: 22 AN XY: 33123

Gnomad AFR AF: 0.0000656

Gnomad AMI AF: 0.00291

Gnomad AMR AF: 0.000292

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00117

Gnomad OTH AF: 0.000672

GnomAD3 exomes AF: 0.000519 AC: 93 AN: 179121 Hom.: 0 AF XY: 0.000515 AC XY: 33 AN XY: 64021

Gnomad AFR exome AF: 0.0000776

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00116

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00160 AC: 1750 AN: 1096559 Hom.: 1 Cov.: 31 AF XY: 0.00143 AC XY: 517 AN XY: 361955

Gnomad4 AFR exome AF: 0.000152

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00202

Gnomad4 OTH exome AF: 0.00104

GnomAD4 genome AF: 0.000631 AC: 70 AN: 110869 Hom.: 0 Cov.: 22 AF XY: 0.000664 AC XY: 22 AN XY: 33123

Gnomad4 AFR AF: 0.0000656

Gnomad4 AMR AF: 0.000292

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00117

Gnomad4 OTH AF: 0.000672

Alfa AF: 0.00145 Hom.: 55

Bravo AF: 0.000714

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00381 AC: 11

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00149 AC: 10

ExAC AF: 0.000404 AC: 49

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1 Benign:2

Uncertain significance, no assertion criteria provided	literature only	OMIM	Aug 08, 2013	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 15, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	ZNF41: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	11
Dann	Benign	0.56
FATHMM_MKL	Benign	0.38	N
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.019	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.82	A;A;A
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.98	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.34	T;T;T
Sift4G	Benign	0.44	T;T;.
Polyphen		0.065	B;B;.
Vest4		0.65
MVP		0.26
MPC		0.25
ClinPred		0.022	T
GERP RS		3.1
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs104894955; hg19: chrX-47308837; COSMIC: COSV57441095;