rs3200401

Variant names:

• chr11-65504361-C-T
• rs3200401
• ENST00000508832.3:n.5077C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000612781.2(MALAT1):​n.1211+3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 516,094 control chromosomes in the GnomAD database, including 8,189 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 0.17 (2317 hom., cov: 31)
  • Exomes 𝑓: 0.17 (5872 hom.)
• Consequence: MALAT1 ENST00000612781.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

Genes affected

MALAT1 (HGNC:29665): (metastasis associated lung adenocarcinoma transcript 1) This gene produces a precursor transcript from which a long non-coding RNA is derived by RNase P cleavage of a tRNA-like small ncRNA (known as mascRNA) from its 3' end. The resultant mature transcript lacks a canonical poly(A) tail but is instead stabilized by a 3' triple helical structure. This transcript is retained in the nucleus where it is thought to form molecular scaffolds for ribonucleoprotein complexes. It may act as a transcriptional regulator for numerous genes, including some genes involved in cancer metastasis and cell migration, and it is involved in cell cycle regulation. Its upregulation in multiple cancerous tissues has been associated with the proliferation and metastasis of tumor cells. [provided by RefSeq, Mar 2015]

TALAM1 (HGNC:54476): (TALAM1 transcript, MALAT1 antisense RNA)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MALAT1	NR_002819.5	n.5317C>T		non_coding_transcript_exon_variant	Exon 1 of 1
MALAT1	NR_144567.1	n.6390C>T		non_coding_transcript_exon_variant	Exon 2 of 2
MALAT1	NR_144568.1	n.6147C>T		non_coding_transcript_exon_variant	Exon 3 of 3
TALAM1	NR_145459.1	n.3072G>A		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MALAT1	ENST00000508832.3	n.5077C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
MALAT1	ENST00000534336.3	n.6722C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
MALAT1	ENST00000610851.2	n.5303C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25322 AN: 150644 Hom.: 2317 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0915

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.167 AC: 38316 AN: 229680 Hom.: 3403 AF XY: 0.167 AC XY: 21218 AN XY: 126700

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.161

Gnomad SAS exome AF: 0.118

Gnomad FIN exome AF: 0.0993

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.172 AC: 62670 AN: 365332 Hom.: 5872 Cov.: 0 AF XY: 0.170 AC XY: 35668 AN XY: 209448

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.168 AC: 25325 AN: 150762 Hom.: 2317 Cov.: 31 AF XY: 0.160 AC XY: 11763 AN XY: 73486

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0915

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.163

Alfa AF: 0.196 Hom.: 3154

Bravo AF: 0.175

Asia WGS AF: 0.125 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3200401; hg19: chr11-65271832; COSMIC: COSV73174580;