rs3822908

chr6-97151736-T-C

Variant summary

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

The NM_001350599.2(MMS22L):c.3482+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,533,606 control chromosomes in the GnomAD database, including 32,324 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 0.19 (3018 hom., cov: 32)
  • Exomes 𝑓: 0.20 (29306 hom.)
• Consequence: MMS22L NM_001350599.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.78

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=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMS22L	NM_001350599.2	c.3482+35A>G		intron_variant		ENST00000683635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMS22L	ENST00000683635.1	c.3482+35A>G		intron_variant			NM_001350599.2	P1
MMS22L	ENST00000275053.8	c.3482+35A>G		intron_variant		2		P1
MMS22L	ENST00000369251.6	c.3362+35A>G		intron_variant		2
MMS22L	ENST00000514790.1	n.176A>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28151 AN: 152062 Hom.: 3006 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.170

GnomAD3 exomes AF: 0.226 AC: 56328 AN: 249248 Hom.: 7656 AF XY: 0.222 AC XY: 29877 AN XY: 134666

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.288

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.524

Gnomad SAS exome AF: 0.234

Gnomad FIN exome AF: 0.209

Gnomad NFE exome AF: 0.180

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.198 AC: 273164 AN: 1381426 Hom.: 29306 Cov.: 20 AF XY: 0.198 AC XY: 136933 AN XY: 691672

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.477

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.185 AC: 28178 AN: 152180 Hom.: 3018 Cov.: 32 AF XY: 0.188 AC XY: 14000 AN XY: 74378

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.180

Alfa AF: 0.183 Hom.: 5189

Bravo AF: 0.190

Asia WGS AF: 0.405 AC: 1408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	0.038
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3822908; hg19: chr6-97599612; COSMIC: COSV51516572;