NM_001350599.2:c.2385-1007C>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350599.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMS22L	NM_001350599.2	MANE Select	c.2385-1007C>A		intron	N/A	NP_001337528.1
	MMS22L	NM_198468.4		c.2385-1007C>A		intron	N/A	NP_940870.2
	MMS22L	NM_001350600.2		c.1536-1007C>A		intron	N/A	NP_001337529.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMS22L	ENST00000683635.1	MANE Select	c.2385-1007C>A		intron	N/A	ENSP00000508046.1
	MMS22L	ENST00000275053.8	TSL:2	c.2385-1007C>A		intron	N/A	ENSP00000275053.4
	MMS22L	ENST00000929352.1		c.2385-1007C>A		intron	N/A	ENSP00000599411.1

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

African (AFR) AF: 0.729 AC: 30235 AN: 41460

American (AMR) AF: 0.471 AC: 7191 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1847 AN: 3472

East Asian (EAS) AF: 0.225 AC: 1165 AN: 5172

South Asian (SAS) AF: 0.574 AC: 2767 AN: 4822

European-Finnish (FIN) AF: 0.434 AC: 4578 AN: 10540

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34752 AN: 67948

Other (OTH) AF: 0.549 AC: 1156 AN: 2106

Alfa AF: 0.533 Hom.: 7849

Bravo AF: 0.556

Asia WGS AF: 0.403 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.10
DANN	Benign	0.35
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1014976; hg19: chr6-97628442;