rs11699738

Variant names:

• chr20-36861937-G-A
• rs11699738
• NM_080627.4:c.687+721C>T

Variant summary

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

The NM_080627.4(MTCL2):​c.687+721C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0554 in 152,316 control chromosomes in the GnomAD database, including 360 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 0.055 (360 hom., cov: 33)
• Consequence: MTCL2 NM_080627.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 4 publications found

Genes affected

MTCL2 (HGNC:16111): (microtubule crosslinking factor 2) Predicted to be involved in insulin receptor signaling pathway; negative regulation of gluconeogenesis; and regulation of autophagy. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTCL2	NM_080627.4	c.687+721C>T		intron_variant	Intron 1 of 14	ENST00000237536.9	NP_542194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTCL2	ENST00000237536.9	c.687+721C>T		intron_variant	Intron 1 of 14	5	NM_080627.4	ENSP00000237536.4

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8442 AN: 152198 Hom.: 360 Cov.: 33

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00952

Gnomad FIN AF: 0.0354

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0554 AC: 8439 AN: 152316 Hom.: 360 Cov.: 33 AF XY: 0.0519 AC XY: 3864 AN XY: 74484

African (AFR) AF: 0.0158 AC: 655 AN: 41580

American (AMR) AF: 0.0349 AC: 534 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.00953 AC: 46 AN: 4828

European-Finnish (FIN) AF: 0.0354 AC: 376 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0963 AC: 6550 AN: 68014

Other (OTH) AF: 0.0369 AC: 78 AN: 2112

Alfa AF: 0.0784 Hom.: 926

Bravo AF: 0.0534

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.65
PhyloP100		0.041
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11699738; hg19: chr20-35490340;