rs1206164

chr6-97148471-G-Achr6-97148471-G-Cchr6-97148471-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350599.2(MMS22L):c.3650+1382C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,010 control chromosomes in the GnomAD database, including 50,032 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 0.80 (50032 hom., cov: 30)
• Consequence: MMS22L NM_001350599.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

Genes affected

MMS22L (HGNC:21475): (MMS22 like, DNA repair protein) The protein encoded by this gene forms a complex with tonsoku-like, DNA repair protein (TONSL), and this complex recognizes and repairs DNA double-strand breaks at sites of stalled or collapsed replication forks. The encoded protein also can bind with the histone-associated protein NFKBIL2 to help regulate the chromatin state at stalled replication forks. Finally, this gene appears to be overexpressed in most lung and esophageal cancers. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMS22L	NM_001350599.2	c.3650+1382C>T		intron_variant		ENST00000683635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMS22L	ENST00000683635.1	c.3650+1382C>T		intron_variant			NM_001350599.2	P1
MMS22L	ENST00000275053.8	c.3650+1382C>T		intron_variant		2		P1
MMS22L	ENST00000369251.6	c.3530+1382C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122048 AN: 151892 Hom.: 49965 Cov.: 30

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.804 AC: 122175 AN: 152010 Hom.: 50032 Cov.: 30 AF XY: 0.808 AC XY: 60008 AN XY: 74312

Gnomad4 AFR AF: 0.949

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.794

Alfa AF: 0.774 Hom.: 7786

Bravo AF: 0.820

Asia WGS AF: 0.946 AC: 3286 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.7
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1206164; hg19: chr6-97596347;