chr10-97462918-A-C

Variant names:

• chr10-97462918-A-C
• rs29001322
• NM_022362.5:c.1913-236T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022362.5(MMS19):​c.1913-236T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MMS19 NM_022362.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812
• Publications: 6 publications found

Genes affected

MMS19 (HGNC:13824): (MMS19 homolog, cytosolic iron-sulfur assembly component) Enables estrogen receptor binding activity and transcription coactivator activity. Involved in several processes, including iron-sulfur cluster assembly; positive regulation of nucleobase-containing compound metabolic process; and protein maturation by iron-sulfur cluster transfer. Located in cytosol; nucleoplasm; and spindle. Part of CIA complex and MMXD complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022362.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMS19	NM_022362.5	MANE Select	c.1913-236T>G		intron	N/A	NP_071757.4
	MMS19	NM_001351356.2		c.2030-236T>G		intron	N/A	NP_001338285.1
	MMS19	NM_001289405.2		c.1913-236T>G		intron	N/A	NP_001276334.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMS19	ENST00000438925.7	TSL:1 MANE Select	c.1913-236T>G		intron	N/A	ENSP00000412698.2
	MMS19	ENST00000370782.6	TSL:1	c.1913-236T>G		intron	N/A	ENSP00000359818.1
	MMS19	ENST00000355839.10	TSL:1	c.1784-236T>G		intron	N/A	ENSP00000348097.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 267322 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 137570

African (AFR) AF: 0.00 AC: 0 AN: 7500

American (AMR) AF: 0.00 AC: 0 AN: 8800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9400

East Asian (EAS) AF: 0.00 AC: 0 AN: 21462

South Asian (SAS) AF: 0.00 AC: 0 AN: 11868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1396

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 169530

Other (OTH) AF: 0.00 AC: 0 AN: 17190

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.81

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: rs29001322; hg19: chr10-99222675;