chr10-38095711-T-G

Variant names:

• chr10-38095711-T-G
• rs2474571
• NM_001324250.3:c.-105-33T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001324250.3(ZNF37A):​c.-105-33T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,086 control chromosomes in the GnomAD database, including 13,075 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.41 (13072 hom., cov: 32)
  • Exomes 𝑓: 0.38 (3 hom.)
• Consequence: ZNF37A NM_001324250.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 7 publications found

Genes affected

ZNF37A (HGNC:13102): (zinc finger protein 37A) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PLD5P1 (HGNC:55072): (PLD5 pseudogene 1) Predicted to be involved in regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000302873 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001324250.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF37A	NM_001324250.3	MANE Select	c.-105-33T>G		intron	N/A	NP_001311179.1
	ZNF37A	NM_001007094.4		c.-105-33T>G		intron	N/A	NP_001007095.1
	ZNF37A	NM_001178101.3		c.-105-33T>G		intron	N/A	NP_001171572.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF37A	ENST00000685332.1	MANE Select	c.-105-33T>G		intron	N/A	ENSP00000508865.1
	ZNF37A	ENST00000351773.7	TSL:1	c.-105-33T>G		intron	N/A	ENSP00000329141.3
	PLD5P1	ENST00000640275.1	TSL:5	n.-105-33T>G		intron	N/A	ENSP00000491560.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62493 AN: 151928 Hom.: 13038 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.375 AC: 15 AN: 40 Hom.: 3 Cov.: 0 AF XY: 0.292 AC XY: 7 AN XY: 24

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.333 AC: 4 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.571 AC: 8 AN: 14

Other (OTH) AF: 0.250 AC: 3 AN: 12

GnomAD4 genome AF: 0.412 AC: 62581 AN: 152046 Hom.: 13072 Cov.: 32 AF XY: 0.407 AC XY: 30247 AN XY: 74344

African (AFR) AF: 0.415 AC: 17202 AN: 41448

American (AMR) AF: 0.467 AC: 7135 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1401 AN: 3472

East Asian (EAS) AF: 0.499 AC: 2573 AN: 5158

South Asian (SAS) AF: 0.249 AC: 1201 AN: 4830

European-Finnish (FIN) AF: 0.315 AC: 3330 AN: 10584

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28422 AN: 67966

Other (OTH) AF: 0.426 AC: 899 AN: 2112

Alfa AF: 0.414 Hom.: 1702

Bravo AF: 0.430

Asia WGS AF: 0.406 AC: 1412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		-2.6
BranchPoint Hunter		0.0
RBP_binding_hub_radar		0.91
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2474571; hg19: chr10-38384639;