6-97148471-G-A

Variant names:

• chr6-97148471-G-A
• rs1206164
• NM_001350599.2:c.3650+1382C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MMS22L	NM_001350599.2	c.3650+1382C>T		intron_variant	Intron 24 of 24	ENST00000683635.1	NP_001337528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMS22L	ENST00000683635.1	c.3650+1382C>T		intron_variant	Intron 24 of 24		NM_001350599.2	ENSP00000508046.1
MMS22L	ENST00000275053.8	c.3650+1382C>T		intron_variant	Intron 24 of 24	2		ENSP00000275053.4
MMS22L	ENST00000369251.6	c.3530+1382C>T		intron_variant	Intron 22 of 22	2		ENSP00000358254.2

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

African (AFR) AF: 0.949 AC: 39373 AN: 41498

American (AMR) AF: 0.823 AC: 12554 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2468 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5163 AN: 5172

South Asian (SAS) AF: 0.875 AC: 4218 AN: 4818

European-Finnish (FIN) AF: 0.671 AC: 7072 AN: 10536

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.717 AC: 48707 AN: 67952

Other (OTH) AF: 0.794 AC: 1674 AN: 2108

Alfa AF: 0.780 Hom.: 8139

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
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1206164; hg19: chr6-97596347;