NM_001100399.2:c.4010+2543T>C

Variant names:

• chr4-39835313-A-G
• rs7657667
• NM_001100399.2:c.4010+2543T>C

Variant summary

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

The NM_001100399.2(PDS5A):​c.4010+2543T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0711 in 152,296 control chromosomes in the GnomAD database, including 485 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.071 (485 hom., cov: 32)
• Consequence: PDS5A NM_001100399.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 2 publications found

Genes affected

PDS5A (HGNC:29088): (PDS5 cohesin associated factor A) The protein encoded by this gene binds to the cohesin complex and associates with chromatin through most of the cell cycle. The encoded protein may play a role in regulating sister chromatid cohesion during mitosis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0996 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDS5A	NM_001100399.2	c.4010+2543T>C		intron_variant	Intron 32 of 32	ENST00000303538.13	NP_001093869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDS5A	ENST00000303538.13	c.4010+2543T>C		intron_variant	Intron 32 of 32	1	NM_001100399.2	ENSP00000303427.8

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10834 AN: 152178 Hom.: 485 Cov.: 32

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.0443

Gnomad ASJ AF: 0.0646

Gnomad EAS AF: 0.0371

Gnomad SAS AF: 0.0842

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0587

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0711 AC: 10835 AN: 152296 Hom.: 485 Cov.: 32 AF XY: 0.0701 AC XY: 5220 AN XY: 74472

African (AFR) AF: 0.0222 AC: 924 AN: 41576

American (AMR) AF: 0.0442 AC: 676 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0646 AC: 224 AN: 3470

East Asian (EAS) AF: 0.0372 AC: 193 AN: 5186

South Asian (SAS) AF: 0.0846 AC: 409 AN: 4832

European-Finnish (FIN) AF: 0.111 AC: 1182 AN: 10618

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6906 AN: 68000

Other (OTH) AF: 0.0581 AC: 123 AN: 2116

Alfa AF: 0.0890 Hom.: 928

Bravo AF: 0.0622

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-0.27
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: rs7657667; hg19: chr4-39836933;