6-97180566-G-T

Variant names:

• chr6-97180566-G-T
• rs1014976
• NM_001350599.2:c.2385-1007C>A

Variant summary

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

The NM_001350599.2(MMS22L):​c.2385-1007C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,006 control chromosomes in the GnomAD database, including 24,532 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 0.56 (24532 hom., cov: 32)
• Consequence: MMS22L NM_001350599.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMS22L	NM_001350599.2	c.2385-1007C>A		intron_variant	Intron 16 of 24	ENST00000683635.1	NP_001337528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMS22L	ENST00000683635.1	c.2385-1007C>A		intron_variant	Intron 16 of 24		NM_001350599.2	ENSP00000508046.1
MMS22L	ENST00000275053.8	c.2385-1007C>A		intron_variant	Intron 16 of 24	2		ENSP00000275053.4
MMS22L	ENST00000369251.6	c.2265-1007C>A		intron_variant	Intron 14 of 22	2		ENSP00000358254.2

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84335 AN: 151888 Hom.: 24478 Cov.: 32

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.555 AC: 84419 AN: 152006 Hom.: 24532 Cov.: 32 AF XY: 0.552 AC XY: 41001 AN XY: 74266

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.549

Alfa AF: 0.525 Hom.: 5843

Bravo AF: 0.556

Asia WGS AF: 0.403 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.10
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs1014976; hg19: chr6-97628442;